(BQ) Part 2 book Principles and practice of PET and PET/CT presents the following contents: Neurologic applications, psychiatric disorders, cardiac applications, PET/CT imaging of infection and inflammation, PET and drug development, PET Imaging as a biomarker, emerging opportunities.
LWBK053-3787G-9.01[479-499].qxd 14-08-2008 05:56 PM Page 479 Aptara Inc CHAPTER 9.1 Movement Disorders, Stroke, and Epilepsy NICOLAAS I BOHNEN GENERAL PRINCIPLES OF CEREBRAL BLOOD FLOW AND METABOLIC IMAGING: FUNCTIONAL COUPLING AND PHYSIOLOGICAL CORRELATES READING BRAIN PET IMAGES: NORMAL VARIANTS, AGING, AND OTHER FACTORS THAT MAY AFFECT BLOOD FLOW OR GLUCOSE METABOLISM Normal Variants Normal Aging: From Infancy to Adulthood Normal Aging: From Adulthood to the Elderly Factors that May Affect Resting Cerebral Blood Flow or Glucose Metabolic Studies Diaschisis: Remote Functional Effects of Focal Brain Lesions MOVEMENT DISORDERS Parkinson Disease Parkinsonian or Lewy Body Dementia Progressive Supranuclear Palsy Corticobasal Degeneration Multiple System Atrophy Essential Tremor Huntington Disease and Choreiform Movement Disorders Dopaminergic Neurochemical Imaging: Diagnosis of Parkinson Disease Pre- and Postsynaptic Dopaminergic Neurochemical Imaging: Atypical Parkinsonian Disorders Dopaminergic Neurochemical Imaging: Differential Diagnosis of Parkinsonian or Lewy Body Dementia from Alzheimer Disease STROKE Measurement of Cerebral Oxygen Metabolism, Cerebral Blood Volume, and Oxygen Extraction Fraction Using PET Acute Ischemic Stroke Subacute Changes in Ischemic Stroke Chronic Arterial Occlusive Disease and Hemodynamic Reserve Hemorrhagic Stroke Estimation of Prognosis After Stroke Clinical Applicability of Multitracer PET in the Management of Patients with Stroke New Emerging Clinical Applications of PET in Stroke: Neuronal and Hypoxia Imaging EPILEPSY Regional Glucose Hypometabolism as Interictal Expression of Epileptogenic Foci Regional Glucose Hypometabolism in Temporal Lobe Epilepsy Extratemporal Epilepsy Glucose Metabolic PET Studies of Children with Infantile Spasms Glucose Metabolic PET Studies in Lennox-Gastaut Syndrome Interictal H2[15O] Cerebral Blood Flow PET Studies Ictal PET Mapping of Cognitive or Language Functions Emerging Clinical Applications of Benzodiazepine Neuroreceptor and Serotonin Synthesis Imaging in Epilepsy CONCLUSION natomic imaging, such as computed tomography (CT) and magnetic resonance imaging (MRI), has revolutionized the diagnosis and management of the neurological patient However, a brain lesion may be present functionally rather than associated with a macroscopic structural abnormality detectable by noninvasive anatomical imaging For example, anatomical imaging in early idiopathic Parkinson disease may not reveal disease-specific changes, while positron emission tomography (PET) has clearly demonstrated the dopaminergic system abnormalities in this disorder PET is a molecular imaging technique that uses radiolabeled molecules to image molecular interactions of biological processes in vivo Low doses of positron emitting radiotracers are being used for the radiolabeling of molecules or drugs that have binding sites in the brain, such as receptors, follow regional cerebral blood flow, or are metabolized by cerebral enzymes PET can be used to perform neurochemical and functional brain imaging studies of cerebral blood flow or glucose metabolism Neurochemical imaging studies allow assessment of the regional distribution and quantitative measurement of neurotransmitters, enzymes, or receptors in the living brain Neurochemical imaging studies are mainly performed for research purposes Functional brain imaging studies can measure regional cerebral blood flow or glucose metabolism These studies may be performed in the resting state or following a specific intervention (e.g., a mental task, sensory stimulus or motor task) to “activate” specific regions in the brain A 479 LWBK053-3787G-9.01[479-499].qxd 14-08-2008 05:56 PM Page 480 Aptara Inc 480 Principles and Practice of PET and PET/CT Imaging of resting glucose metabolism and/or blood flow in the brain represent the major clinical applications of PET in neurology and will be mainly discussed in this chapter The recent introduction of PET/CT into clinical practice may have limited utility when evaluating small lesions that are better visualized on MRI but offers the advantage of increased spatial accuracy when evaluating normal metabolic variants or artifacts due to partial volume effects In addition, the intrinsically registered nature of the CT images from PET/CT can be helpful in both lesion localization as well as attenuation correction specific for the patient PET studies of specific neurochemical markers, in particular dopamine, will also be discussed when clinically useful or promising The precise correlation of anatomic findings with PET through image fusion is often useful and is facilitated through PET/CT fusion imaging as well as software fusion of PET with MRI images GENERAL PRINCIPLES OF CEREBRAL BLOOD FLOW AND METABOLIC IMAGING: FUNCTIONAL COUPLING AND PHYSIOLOGICAL CORRELATES The energy metabolism of the adult human brain depends almost completely on the oxidation of glucose (1) Because the brain is unable to store either oxygen or glucose, it is thought that regional cerebral blood flow (rCBF) is continuously regulated to supply these substrates locally The functional coupling of rCBF and local cerebral glucose metabolism has been established in a wide range of experiments using autoradiographic techniques in animals as well as double-tracer techniques in humans Increased function of the central neurons results in increased neuronal metabolism and, as a consequence, increased concentration of metabolic end products (Hϩ, Kϩ, adenosine) results in increased rCBF (2) A model has been proposed where neurogenic stimuli via perivascular nerve endings may act as rapid initiators responsible for moment-to-moment dynamic adjustment of rCBF to the metabolic demands (2) Functional activation of the brain (e.g., motor or visual activity) is accompanied by increases in rCBF and glucose consumption but only minimal increases in oxygen consumption (3,4) Therefore, large changes in blood flow are required to support small changes in the oxygen metabolic rate during neuronal stimulation (5) Increased oxygen consumption may result from a combined effect of increased blood flow and increased oxygen diffusion capacity in the region of brain activation (6) Factors other than local requirements in oxygen also underlie the increase in rCBF associated with physiological activation (7) Oxygen-15 radiolabeled water (H2[15O]) is the most commonly used PET tracer for the measurement of rCBF CBF can also be assessed by the inhalation of Oxygen-15 labeled carbon dioxide (C[15O2]) The very short half-life of oxygen-15 [15O] (123 seconds) allows repeated and rapid rCBF assessments in the same individual Fluorine-18 [18F]-fluorodeoxyglucose (FDG) is a PET tracer used for the study of regional cerebral glucose metabolism The majority of glucose in the brain is needed for maintenance of membrane potentials and restoration of ion gradients The linking between synaptic activity and glucose utilization is a central physiological principle of brain function that has provided the basis for FDG brain PET imaging (8) Although the FDG PET signal represents neuronal and more specifically synaptic activity (9), glutamate-mediated uptake of the radioligand into astrocytes also appears to be a major mechanism (10) The basic mechanism involves glutamate-stimulated aerobic glycolysis: the sodium-coupled reuptake of glutamate by astrocytes and the ensuing activation of the sodium-potassium-adenosine triphosphatase (Na-K-ATPase) triggers glucose uptake and processing via glycolysis, resulting in the release of lactate from astrocytes Lactate can then contribute to the activity-dependent fueling of the neuronal energy demands associated with synaptic transmission An operational model, the astrocyte-neuron lactate shuttle, is supported experimentally by a large body of evidence, which provides a molecular and cellular basis for interpreting data obtained from functional brain imaging studies (8) In addition, this neuronglia metabolic coupling undergoes plastic adaptations in parallel with adaptive mechanisms that characterize synaptic plasticity (8) READING BRAIN PET IMAGES: NORMAL VARIANTS, AGING, AND OTHER FACTORS THAT MAY AFFECT BLOOD FLOW OR GLUCOSE METABOLISM The spatial resolution of the PET camera determines the extent of the partial volume effect that causes the edges of small brain structures to blur one another due to averaging of radioactivity Therefore, the size of the imaged structure determines the recovery of counts by the camera from that structure (11) A structure must have dimensions greater than twice the resolution of the PET camera at full width half maximum in order to recover 100% of true tissue activity from that structure Partial volume effects may give a blurred or smoothed scan appearance of small brain structures, atrophied gyri, and smaller brain volumes, such as the inferior orbitofrontal and inferior temporal regions Conversely, a cerebral sulcus, where two gray matter gyri face each other closely, may show relatively higher activity when a scanner does not have sufficient spatial resolution to resolve the two gyri (12) For instance, the pre- and postcentral gyri opposed at the central sulcus may form a single focus of relatively high activity (12) Similarly, the adjacent areas of the insular cortex and the superior temporal gyral cortex generate sufficiently similar FDG activity so that they may appear as one lateral mass at certain levels of scanning (13) Higher resolution PET cameras can help in this regard and are available in some centers It should be noted that a normal individual’s brain is not completely symmetric For example, the sylvian fissure in right-handed individuals is longer and more horizontal in the left hemisphere Normal irregularity of gyral convolutions may give a heterogeneous scan appearance Therefore, a commonly observed rule of visual PET analysis is the requirement that an area of apparent functional alteration of a brain structure should be seen on at least several adjacent slices in order to be deemed significant (13) Further, direct correlation with an anatomic imaging study is often required to recognize normal structural variability Studies of left-to-right hemispheric asymmetries in normal subjects are limited and have not been conclusive An rCBF PET study reported slightly higher mean right hemispheric flow compared to left-sided values (14) An rCBF single-photon computed emission tomography (SPECT) study demonstrated consistent hemispheric asymmetry (right side greater than left side) in the cuneus, occipital cortex, occipital pole, middle temporal gyrus, and posterior middle frontal gyrus in 83% to 100% of individuals (15) LWBK053-3787G-9.01[479-499].qxd 14-08-2008 05:56 PM Page 481 Aptara Inc Chapter 9.1 • Movement Disorders, Stroke, and Epilepsy FIGURE 9.1.1 PET images showing normal glucose metabolic variants in healthy volunteers Examples of more prominent uptake in the frontal eye fields (A), posterior cingulate cortex (B), and an area of more intense uptake in the posterior parietal lobe (C) are shown by arrows The angular gyrus is demonstrated by the dashed arrow in image C A, B C FDG PET studies have indicated that hemispheric asymmetries may depend on whether subjects are studied with open versus closed eyes or ears that are covered (16) For example, studies performed on subjects with eyes closed and ears covered demonstrated greater left than right hemispheric glucose metabolism Subjects studied with closed eyes and ears also had a progressive overall decrease in glucose metabolism, reflecting general sensory deprivation (16) Decreased tracer uptake in the visual cortex is typical as well in patients whose eyes are covered Normal Variants There are several normal variants that should be recognized when interpreting cerebral metabolic or blood flow PET scans Some normal brain regions have focally more prominent metabolic or flow activity These include the frontal eye fields (which can be asymmetric), posterior cingulate cortex and adjacent angular gyrus, Wernicke’s region, the visual cortex (when subjects are injected with the eyes open), and an area of more intense uptake in the posterior parietal lobe (Fig 9.1.1) (17,18) The frontal eye fields have an approximate dimension of about cm and are located a few centimeters anterior to the primary motor cortex (17) Wernicke’s region is defined as an area of moderately intense activity measuring a few centimeters in size and is located in the posterior-superior temporal lobe The posterior cingulate cortex is situated superior and anterior to the occipital cortex An area of focally intense activity in the posterior parietal region is seen in about 50% of the normal population and appears mostly symmetric (Table 9.1.1) (17,18) Basal ganglia to cortex TA B L E Frontal eye field Wernicke’s area Posterior parietal lobe 481 Frequency of Prominent Normal Fluorodeoxyglucose Brain PET Variants in the General Population Right (%) Left (%) 84 80 58 77 85 46 (From Loessner A, Alavi A, Lewandrowski KU, et al Regional cerebral function determined by FDG-PET in healthy volunteers: normal patterns and changes with age J Nucl Med 1995;36:11411149, with permission.) ratios are greater than unity, indicating relatively higher activity in the basal ganglia compared to the average cortex (17) Some brain regions, like the very anterior aspect of the frontal poles, may have less prominent or decreased tracer uptake (17) Normal Aging: From Infancy to Adulthood CBF PET studies in children have shown lower flow values in neonates compared to older children (19) The rCBF will reach adult values during adolescence (19) No major difference in rCBF has been observed between the basal ganglia and cortical gray matter in children with the exception of more prominent occipital flow FDG metabolic studies in infants and children have shown that infants less than weeks old have highest metabolic activity in the sensorimotor cortex, thalamus, brainstem, and cerebellar vermis By months, metabolic activity increases in parietal, temporal, and occipital cortices, basal ganglia, and cerebellar cortex (20) Frontal and dorsolateral occipital cortical regions display a maturational rise in glucose metabolic activity by approximately to months Absolute values of glucose metabolic rate for various gray matter regions are low at birth (13 to 25 mol/min/100 g), and rapidly rise to reach adult values (19 to 33 mol/min/100 g) by years Glucose metabolic rate continues to rise until, by to years, reaching values of 49 to 65 mol/min/100 g in most regions (20) These high rates are maintained until approximately years, when they begin to decline, and reach adult rates again by the latter part of the second decade The highest increases over adult values have been noted in cerebral cortical structures Lesser increases have been found to be present in the basal ganglia and cerebellum This time course of metabolic change matches the process describing initial overproduction and subsequent elimination of excessive neurons, synapses, and dendritic spines known to occur in the developing brain An FDG PET study of infants during the first months of life reported glucose metabolic rates for various cortical brain regions and the basal ganglia to be low at birth (from to 16 mol/min/100 g) (21) In infants months of age and younger rates were highest in the sensorimotor cortex, thalamus, and brainstem By months, rates had increased in the frontal, parietal, temporal, occipital, and cerebellar cortical regions In general, the whole brain glucose metabolic activity correlated with postconceptional age, reflecting the functional maturation of these brain regions (21) A statistical brain mapping study of metabolic aging from to 38 years found greatest age-associated changes in the thalamus and anterior cingulate cortex (22) These findings were explained by relative LWBK053-3787G-9.01[479-499].qxd 14-08-2008 05:56 PM Page 482 Aptara Inc 482 Principles and Practice of PET and PET/CT increase of synaptic activities in the thalamus, possibly as a consequence of improved corticothalamic connections Knowledge of the changing metabolic patterns during normal brain development is a necessary prelude to the study of abnormal brain development Normal Aging: From Adulthood to the Elderly Postmortem studies have shown relatively stable neuronal numbers but loss in cell size and a decreased number of glial cells with advancing age (23) However, it remains a matter of controversy as to whether cerebral perfusion declines with healthy aging H2[15O] rCBF PET studies have shown a negative correlation between age and rCBF in the mesial frontal cortex, involving the anterior cingulate region (24) Age-related flow decreases have also been reported for the cingulate, parahippocampal, superior temporal, medial frontal, and posterior parietal cortices bilaterally, and in the left insular and left posterior prefrontal cortices (25) It should be realized that the affected areas represent limbic or neocortical association areas and, therefore, bias from possible preclinical dementia cannot be excluded It has been suggested that lack of partial volume correction for the dilution effect of age-related cerebral volume loss on PET measurements may be another reason for the observed age-related decline For example, one study found a significant difference in mean cortical CBF between young/midlife (age range, 19 to 46 years; mean Ϯ standard deviation [SD], 56 Ϯ 10 mL/100 mL/min) and elderly (age range, 60 to 76 years; mean Ϯ SD, 49 Ϯ 2.6 mL/100 mL/min) subgroups before correcting for partial-volume effects (26) However, this group difference resolved after partial-volume correction (young/midlife: mean Ϯ SD, 62Ϯ 10 mL/100 mL/min; elderly: mean Ϯ SD, 61 Ϯ 4.8 mL/100 mL/min) FDG PET imaging studies have shown decreased cortical metabolism with normal aging, particularly in the frontal lobes (17) Temporal, parietal, and occipital lobe metabolism varied considerably among subjects within the same age group as well as over decades (17) Basal ganglia, hippocampal area, thalami, cerebellum, posterior cingulate gyrus, and visual cortex remained metabolically unchanged with advancing age (17) An FDG PET study found bilateral medial prefrontal, including anterior cingulate cortices, and dorsolateral prefrontal reductions with normal aging (27) Brain scans of the aging and atrophied brain will demonstrate widened cerebral sulci, increased separation of the caudate nuclei and thalami, as well as widening of the anterior fissure However, a Japanese study found that age-associated metabolic reductions that were present in bilateral perisylvian and medial frontal regions largely resolved after correction for partial volume effects (28) (watching a movie) led to significant glucose metabolic increases in visual and auditory cortical areas but significant decreases in frontal areas in normal volunteers (29) Metabolic factors,such as hyperglycemia,may impair cortical FDG uptake (30) Therefore, knowledge of the clinical or behavioral state of the patient at the time of the injection and study is critical for proper image interpretation As with any nuclear medicine study, better image quality will depend on improved count statistics Since PET images are an average of radioactivity over a certain period of time, FDG acquisitions taken over 10 to 30 minutes will lead to better image quality compared to short-lasting (1 to minutes) H2[15O] CBF studies Drugs are also known to induce cerebral blood flow or glucose metabolic changes For example, diazepam sedation has been found to reduce cerebral glucose metabolism globally by about 20% (31) A study by Wang et al (32) found that lorazepam significantly decreased whole-brain metabolism over 10% However, regional effects of lorazepam were largest in the thalamus and occipital cortex (about 20% reduction) An FDG PET study of propofol sedation in children found significant hypometabolism in the medial parieto-occipital cortex bilaterally, including the lingual gyrus, cuneus, and middle occipital gyrus (33) The bilateral parieto-occipital hypometabolism is likely to be a sedation-specific effect and should be taken into account when evaluating cerebral FDG PET scans in sedated patients Antiepileptic drugs have also been found to reduce glucose metabolism and rCBF Studies of valproate have shown global FDG (9% to 10%) and global CBF (about 15%) reductions with greatest regional reductions in the thalamus (34) Phenytoin has been found to cause an average reduction of cerebral glucose metabolism by 13% (35) Cerebellar metabolism may also be reduced by phenytoin, although the effect of the drug is probably less than that due to early onset of uncontrolled epilepsy (Fig 9.1.2) (36,37) Lamotrigine may cause regional cerebral hypometabolism in the bilateral thalami, basal ganglia, and multiple regions of the cerebral cortex (38) Studies of the barbiturate phenobarbital and cerebral glucose metabolism have shown very prominent global reductions of about 37% (39) Neuroleptic drugs can cause differential regional metabolic effects For example, haloperidol caused cerebellar and putaminal glucose metabolic increases, while significant reductions were evident in the frontal, occipital, and anterior cingulate cortex in normal volunteers (40) Factors that May Affect Resting Cerebral Blood Flow or Glucose Metabolic Studies A number of other factors need to be considered when interpreting brain PET images Metabolism or blood flow activity will be most prominent in gray matter when compared to white matter (about four times higher) It should be emphasized that brain glucose metabolic or blood flow PET images are functional in nature For example, if a patient is moving or talking around the time of injection, increased activity in specific brain regions like the basal ganglia, motor cortex, or language centers may be present Subjects studied with eyes open will have increased metabolic activity in the visual cortex when compared to a baseline with the eyes closed (16) An FDG PET study found that passive audiovisual stimulation FIGURE 9.1.2 A fluorodeoxyglucose PET image of a patient with epilepsy showing bilateral cerebellar hypometabolism Cerebellar hypometabolism may be caused by phenytoin therapy, although the effect of the drug is probably less than that due to early onset of uncontrolled epilepsy LWBK053-3787G-9.01[479-499].qxd 14-08-2008 05:56 PM Page 483 Aptara Inc Chapter 9.1 • Movement Disorders, Stroke, and Epilepsy Diaschisis: Remote Functional Effects of Focal Brain Lesions MOVEMENT DISORDERS The functional nature of PET images may reveal metabolic or blood flow changes as a result of focal disturbance in another remote but functionally connected brain region This phenomenon of remote effect is called diaschisis and was originally recognized by Von Monakow (41) in 1914 (42) Diaschisis in the cerebellum was first described by Baron and Marchal (43) in a patient whose PET study showed cerebellar hypoperfusion contralateral to a supratentorial stroke Remote metabolic depression is characterized by coupled reductions in perfusion and metabolism in brain structures remote from, but connected with, the area damaged by a structural lesion This effect has been explained as depressed synaptic activity as a result of disconnection (either direct or transneural) (44) Thus, remote effects allow mapping of the disruption in distributed networks as a result of a focal brain lesion Diaschisis may also occur as subcorticocortical effects Subcorticocortical effects may lead to clinical symptoms, like subcortical aphasia due to thalamic or thalamocapsular stroke Right-sided subcortical lesions may present with left hemineglect (subcortical neglect) (43) Small thalamic infarcts may induce metabolic depression of the ipsilateral cortical mantle (thalamocortical diaschisis) (45) Striatal and thalamic hypometabolism ipsilateral to corticosubcortical stroke is a frequent finding Thalamic hypometabolism may develop a few days after a stroke and presumably represents retrograde degeneration of damaged thalamocortical neurons, whereas striatal hypometabolism probably reflects loss of glutamatergic input from the cortex (43) Crossed cerebrocerebellar diaschisis may occur as early as hours after stroke, is closely related to the volume of supratentorial hypoperfusion, and might be reversible (46) Persistence of diaschisis after stroke is strongly associated with outcome (46) SPECT studies performed as ictal studies during seizure activity have demonstrated a pattern called reverse crossed cerebrocerebellar diaschisis where a supratentorial ictal seizure focus of hyperperfusion is associated with contralateral cerebellar hyperperfusion (Fig 9.1.3) (47) This phenomenon also can be detected with PET PET imaging of cerebral blood flow, metabolic pathways, or neurotransmission systems has contributed to researchers’ understanding of the pathophysiology of movement disorders PET measurements of dopaminergic pathways in the brain have confirmed the importance of dopamine and the basal ganglia in the pathophysiology of movement disorders, such as Parkinson disease Brain activation studies can be performed using CBF or FDG PET These studies compare regional brain activity during specific motor or mental tasks compared to control conditions Activation studies have shown that the basal ganglia are activated whenever movements are performed, planned, or imagined (48) These studies support the existence of functionally independent distributed basal ganglia frontal loops The caudate–prefrontal loop appears to mediate novel sequence learning, problem solving, and movement selection, while the putamen–premotor loop may facilitate automatic sequential patterns of limb movement and implicit acquisition of motor skills (48) Patients with movement disorders may have abnormal blood flow or metabolism in the basal ganglia (Table 9.1.2) Cortical changes may represent primary cortical abnormalities or deafferentation effects because of subcortical abnormalities Patients with movement disorders who also develop dementia typically will show more widespread cortical metabolic or blood flow changes Table 9.1.3 provides a summary of the major subcortical and cortical glucose metabolic changes in neurodegenerative movement disorders Parkinson Disease Parkinson disease is a clinical syndrome consisting of a variable combination of symptoms of tremor, rigidity, postural imbalance, and bradykinesia (49,50) Although Parkinson disease accounts for most patients who have parkinsonian symptoms, parkinsonism can be seen with neurodegenerative disorders other than Parkinson disease, such as progressive supranuclear palsy (PSP) or multiple system atrophy (MSA) (49) Idiopathic Parkinson disease distinguishes itself from other parkinsonian syndromes by marked left–right asymmetry in symptom severity and good symptomatic response to levodopa therapy (49,50) The additional presence of certain clinical findings may raise the clinical suspicion for an atypical parkinsonian syndrome, such as prominent autonomic dysfunction, cerebellar symptoms, or abnormal eye movements (49) TA B L E Examples of Disorders or Conditions with Altered Glucose Metabolism of the Basal Ganglia Increased fluorodeoxyglucose (FDG) metabolic activity basal ganglia A 483 B FIGURE 9.1.3 A: A diagrammatic representation of crossed cerebrocerebellar diaschisis showing cerebellar hypoperfusion contralateral to a supratentorial structural lesion B: Reverse crossed cerebrocerebellar diaschisis can be observed during ictal seizure activity where a supratentorial ictal focus of hyperperfusion is associated with contralateral cerebellar hyperperfusion Decreased FDG metabolic activity basal ganglia Early Parkinson disease Hepatocerebral degeneration Neuroleptic drug effects HIV infection Atypical parkinsonism, such as progressive supranuclear palsy, multiple system atrophy or corticobasal degeneration Wilson disease LWBK053-3787G-9.01[479-499].qxd 14-08-2008 05:56 PM Page 484 Aptara Inc 484 Principles and Practice of PET and PET/CT TA B L E Main Regional Subcortical and Cortical Glucose Metabolic Changes in Neurodegenerative Movement Disorders PD (early) Caudate nucleus Putamen Thalamus Cortex c a T (occipital) PD Dementia Huntington PSP T normal/T TT T TT (esp temporoparietal, precuneus, occipital) T (with dementia) T T T T T T (esp frontal) Midbrain Pons Cerebellum MSA CBD Ta Ta Ta T (frontoparietal) TT TT TT PD, Parkinson disease; PSP, progressive supranuclear palsy; MSA, multiple system atrophy; CBD, (15) corticobasal degeneration a Contralateral to (most) involved body side The clinical features of Parkinson disease to a large degree result from loss of nigrostriatal nerve terminals in the striatum secondary to the degeneration of dopamine-producing pigmented neurons in the substantia nigra in the brainstem (51,52) The greater the neuronal loss in the substantia nigra, the lower the concentration of dopamine in the striatum, and the more severe the parkinsonian symptoms It should be noted that the cellular component of nigrostriatal nerve terminals within the striatum is far less than the number of intrinsic striatal interneurons and projection neurons Therefore, resting glucose metabolic studies primarily reflect the synaptic activity of interneurons and only to a lesser extent afferent projection neurons Resting glucose metabolic and cerebral blood flow studies of patients with early Parkinson disease have shown increased striatal activity contralateral to the clinically most affected body side, which may represent a compensatory mechanism of intrinsic striatal cells (53,54) However, striatal glucose metabolism may decrease with advancing disease (55,56) FDG PET studies have also been used to predict levodopa response in parkinsonian patients A study found that relatively increased FDG activity in the striatum contralateral to the clinically most affected body side was associated with a good levodopa response In contrast, relatively decreased striatal FDG uptake was associated with poor levodopa responsiveness (57) Parkinsonian or Lewy Body Dementia Alzheimer disease is the most common type of dementia The second most common form of degenerative dementia in most clinical series is parkinsonian or Lewy body dementia (58) An arbitrary but generally accepted distinction has been made in current international consensus diagnostic criteria between patients presenting with parkinsonism prior to the onset of dementia (Parkinson disease dementia) and developing parkinsonism and dementia concurrently (dementia with Lewy bodies) (59–61) These durationbased criteria would diagnose patients with Parkinson disease who subsequently develop dementia more than year after their initial Parkinson disease motor symptoms as Parkinson disease dementia Patients meeting the 1-year rule between the onset of dementia and parkinsonism would be diagnosed as dementia with Lewy bodies (60) Although there are relative differences in temporal manifestation and relative severity of clinical symptoms between these clinically defined subgroups of parkinsonian dementia, the underlying neuropathological findings are more similar than dissimilar and suggest these subgroups should be grouped together (62) Parkinsonian dementia is characterized neuropathologically by neuronal losses and Lewy body inclusions in midbrain dopaminergic nuclei (as in Parkinson disease), but involving limbic and neocortical regions as well (58,60) Cortical neuropathologic changes in Alzheimer disease are heterogeneous topographically but are not randomly distributed It has been demonstrated that primary somatosensory and motor cortical regions are relatively spared, while association cortices are more severely involved (63) In the Alzheimer brain, FDG PET imaging reveals characteristic hypometabolism in neocortical structures, especially in posterior cingulate/precuneus, parietal, temporal, and to a lesser and more variable degree in frontal association cortices, the same locations where coexisting cortical neuronal degeneration is also found in postmortem studies (64,65) Parietotemporal hypometabolism can also be seen with parkinsonian or Lewy body dementias Vander Borght et al (56) compared metabolic differences between Alzheimer disease and parkinsonian dementia matched for severity of dementia and found similar glucose metabolic reductions globally and regionally, involving the lateral parietal, lateral temporal, lateral frontal association cortices, and posterior cingulate gyrus when compared to controls However, patients with parkinsonian dementia had greater metabolic reductions in the primary visual cortex and relatively preserved metabolism in the medial temporal lobe Decreased occipital metabolism has also been observed in nondemented patients with Parkinson disease (66) Patients with Alzheimer disease showed only mild reductions in the visual cortex but relatively more pronounced reduction in the medial temporal lobe Metabolic reduction in the posterior cingulate cortex and precuneus demonstrated in Alzheimer disease has also been found in parkinsonian dementia (56) (Table 9.1.4) LWBK053-3787G-9.01[479-499].qxd 14-08-2008 05:56 PM Page 485 Aptara Inc Chapter 9.1 • Movement Disorders, Stroke, and Epilepsy TA B L E 485 Metabolic Differences Between Alzheimer Disease and Parkinsonian Dementia Lateral parietal cortex Lateral temporal cortex Lateral frontal cortex Posterior cingulate cortex Medial temporal cortex Visual cortex Alzheimer Disease Parkinsonian Dementia T T T T T “sparing” T T T T “sparing” T There are similar glucose metabolic reductions globally and regionally involving the lateral parietal, lateral temporal, lateral frontal association cortices, and posterior cingulate gyrus when compared to controls However, patients with parkinsonian dementia have greater metabolic reductions in the primary visual cortex and relatively preserved metabolism in the medial temporal lobe In contrast, patients with Alzheimer disease showed only mild reductions in the visual cortex but relatively more pronounced hypometabolism in the medial temporal lobe (From Vander Borght T, Minoshima S, Giordani B, et al Cerebral metabolic differences in Parkinson’s and Alzheimer’s disease matched for dementia severity J Nucl Med 1997;38:797–802, with permission.) Progressive Supranuclear Palsy PSP or Steele-Richardson-Olszewski syndrome is an atypical parkinsonian syndrome characterized by severe gait and balance disturbances, abnormal eye movements (especially vertical supranuclear gaze palsy), and pseudobulbar palsy More advanced disease is often associated with a frontal lobe type of dementia Pathological changes consist of neurofibrillary tangle formation and neuronal loss in the superior colliculi, brainstem nuclei, periaqueductal gray matter, and basal ganglia (67) PET studies of patients with progressive supranuclear palsy have shown reduced glucose metabolism in the caudate nucleus, putamen, thalamus, pons, and cerebral cortex, but not in the cerebellum (68) There are significant metabolic reductions in most regions throughout the cerebral cortex but are more prominent in the frontal lobe (Fig 9.1.4) (69) Although frontal metabolism decreases with increasing disease duration, relative frontal hypometabolism has been found to already be present in the early stages of the disease (70) Statistical brain mapping studies have demonstrated decreased glucose metabolism in the anterior cingulate, adjacent supplementary motor area, precentral cortex, middle prefrontal cortex, midbrain tegmentum, globus pallidus, and ventrolateral and dorsomedial nuclei of the thalamus (71,72) Clinical parkinsonian motor scores have been reported to correlate with caudate and thalamic glucose metabolic values (70) These data highlight predominant metabolic impairment in subcorticocortical connections in PSP the hemisphere contralateral to the clinically most affected side This reduction can occur in the dorsolateral frontal, medial frontal, inferior parietal, sensorimotor, and lateral temporal cortex as well as in the corpus striatum and the thalamus in patients with corticobasal degeneration (74–76) Statistical brain mapping analysis of patients with corticobasal degeneration have confirmed the asymmetric glucose metabolic impairment in the putamen, thalamus, precentral, lateral premotor and supplementary motor areas, dorsolateral prefrontal cortex, and parietal cortex (77) A Japanese study found the most prominent loss in the parietal lobe in patients with corticobasal degeneration Corticobasal Degeneration Corticobasal degeneration is an atypical parkinsonian syndrome characterized clinically by marked asymmetric limb rigidity with apraxia Patients may also exhibit alien limb phenomenon, cortical sensory loss, and myoclonus Cognitive functions are relatively well preserved in most patients Neuropathological findings consist of swollen, achromatic, tau-staining Pick bodies that may be present in the inferior parietal, posterior frontal, and superior temporal lobes, dentate nucleus, and substantia nigra (73) FDG PET studies have shown significantly reduced cerebral glucose metabolism in FIGURE 9.1.4 A fluorodeoxyglucose PET image of patient with progressive supranuclear palsy showing prominent frontal hypometabolism LWBK053-3787G-9.01[479-499].qxd 14-08-2008 05:56 PM Page 486 Aptara Inc 486 Principles and Practice of PET and PET/CT Lewy body deposition in the brainstem including the locus ceruleus has been found in a subset of subjects (87,88) A PET study found significant glucose hypermetabolism of the medulla and thalami, but not of the cerebellar cortex in patients with essential tremor during resting conditions (89) CBF PET studies using [15O]-water in patients with essential tremor demonstrated abnormally increased bilateral cerebellar, red nuclear, and thalamic blood flow during tremor (90–93) Therefore, the cerebellum and thalamus appear to play important roles as part of a cerebral circuitry that is abnormally activated during tremor Huntington Disease and Choreiform Movement Disorders FIGURE 9.1.5 A fluorodeoxyglucose PET image of patient with corticobasal degeneration showing regionally prominent asymmetric (right) parietal hypometabolism (78) These results confirm the marked asymmetric cerebral involvement, particularly in the parietal cortex and thalamus, in patients with corticobasal degeneration (Fig 9.1.5) (72,78–80) Multiple System Atrophy MSA is an atypical parkinsonian syndrome covering a clinical spectrum of parkinsonism in variable combination with symptoms of cerebellar ataxia or dysautonomia This group of disorders includes Shy-Drager syndrome (MSA of the dysautonomia type), olivopontocerebellar atrophy (MSA of the cerebellar type), and striatonigral degeneration, which resembles Parkinson disease but does not respond to dopaminergic drugs The pathology of MSA is distinct from Parkinson disease and consists of neuronal loss in the substantia nigra, striatum, cerebellum, brainstem, and spinal cord with argyrophilic and glial inclusions (81) An FDG PET study found reduced caudate, putaminal, cerebellar, brainstem, and frontal and temporal cortical glucose metabolism in patients with MSA compared to normal controls (82) A voxel-based analysis of glucose metabolism found significant hypometabolism in the putamen, pons, and cerebellum in patients with MSA (83) Reductions of cerebellar and brainstem glucose metabolism have been reported to be most prominent in patients with olivopontocerebellar atrophy (84) Although cerebellar and brainstem glucose metabolism correlated with the severity of MRI-measured atrophy, some patients who had no MR evidence of tissue atrophy still showed decreased glucose metabolism in these regions (85) Patients with the striatonigral degeneration subtype had relatively preserved brainstem and cerebellar glucose metabolic rates (85) Essential Tremor Essential tremor represents a variable combination of postural and kinetic tremor It most commonly affects the hands, but also occurs in the head, voice, face, trunk, and lower extremities (86) Postmortem studies have found evidence of cerebellar degeneration; Huntington disease is an autosomal dominant neurodegenerative disorder with complete penetrance (94) The gene for Huntington disease, containing an amplified number of cytosine-adenine-guanine (CAG) trinucleotide repeats, is located on the short arm of chromosome (95) Chorea is the most commonly recognized involuntary movement abnormality in adult patients with Huntington disease, but the presence of psychiatric symptoms and dementia may vary (96) Pathologically, Huntington disease is characterized by marked neuronal loss and atrophy in the caudate nucleus and putamen (97,98) Glucose metabolic PET studies in Huntington disease have demonstrated decreased glucose utilization in the caudate nucleus and putamen even before striatal atrophy is apparent on brain CT or MRI scans (99–101) Metabolic covariance analysis of FDG PET data of patients with Huntington disease not only demonstrated caudate and putaminal hypometabolism, but there were reductions in mediotemporal metabolism as well as relative metabolic increases in the occipital cortex (102) Chorea as a hyperkinetic movement disorder can also be seen with other disorders, such as dentatorubropallidoluysian atrophy, neuroacanthocytosis, or Sydenham chorea Striatal, especially caudate, glucose hypometabolism has been demonstrated in dentatorubropallidoluysian atrophy and neuroacanthocytosis This is similar to Huntington disease but striatal glucose metabolism has been found to be increased in a patient with Sydenham chorea and in a patient with antiphospholipid antibody syndrome and chorea (103–107) Patients with hyperglycemia-induced unilateral basal ganglion lesions with and without hemichorea may have reduced ipsilateral glucose metabolism (108) Dopaminergic Neurochemical Imaging: Diagnosis of Parkinson Disease The basal ganglia and the neurotransmitter dopamine have been key targets for research exploring the pathophysiology underlying movement disorders Dopaminergic neurons from the substantia nigra project as nigrostriatal nerve terminals to the striatum where they have synaptic connections with striatal interneurons or projection neurons Presynaptic nigrostriatal dopaminergic activity can be imaged using PET radiotracers like [18F]-fluorodopa (FDOPA) or dopamine transporter protein ligands, such as the cocaine analogue [11C]-WIN35428 (Fig 9.1.6) (109–111) Postsynaptic dopamine D2 receptor binding can be imaged using the PET tracer [11C]raclopride (112) PET studies using presynaptic dopaminergic tracers have objectively demonstrated nigrostriatal nerve terminal loss in Parkinson disease even at a very early or preclinical stage of the disease (113) LWBK053-3787G-9.01[479-499].qxd 14-08-2008 05:56 PM Page 487 Aptara Inc Chapter 9.1 • Movement Disorders, Stroke, and Epilepsy FIGURE 9.1.6 A schematic overview of the nigrostriatal dopamine nerve terminal and a postsynaptic dopamine neuron Dopamine metabolism (DOPA decarboxylase enzyme activity), vesicular monoamine transporter type (VMAT2), synaptic membrane dopamine transporter, and postsynaptic dopamine receptor type and activity can be studied by PET neurochemical imaging Reductions are more severe in the posterior putamen (when compared to the anterior putamen and caudate nucleus) and contralateral to the clinically most affected body side (Fig 9.1.7) (114,115) Putaminal FDOPA uptake is also correlated with clinical measures of disease severity, particularly bradykinesia (54,116–118) Therefore, these techniques can provide neurochemical markers to follow progression of disease or evaluate the effects of therapeutic or neurorestorative interventions For example, fiber outgrowth from transplanted embryonic dopamine neurons, as indicated by an increase in putaminal FDOPA uptake, was detected in patients with severe Parkinson disease (119) Pre- and Postsynaptic Dopaminergic Neurochemical Imaging: Atypical Parkinsonian Disorders Nigrostriatal denervation is not specific for Parkinson disease Presynaptic dopaminergic denervation has also been demonstrated in patients with multiple system atrophy, PSP, corticobasal degeneration, or spinocerebellar atrophy (120–122) Imaging of nigrostriatal dopaminergic system in PSP reveals consistent reductions, with relative regional differences in the intrastriatal pattern of denervation in comparison to Parkinson disease (121,123–127) For example, FIGURE 9.1.7 Carbon-11(ϩ) dihydroletrabenazine (DTBZ) PET images of a normal person (left), patient with Parkinson disease (middle), and parkinsonian dementia (right) There is prominent predominant posterior putaminal (arrow) and asymmetric (dashed arrow) dopaminergic denervation in the patient with Parkinson disease The patient with parkinsonian dementia has more diffuse and bilateral striatal dopaminergic denervation involving both the putamen and caudate nucleus 487 Ilgin et al (128) found that striatal dopamine transporter reductions were more pronounced in the posterior putamen in patients with Parkinson disease, while patients with PSP had a relatively uniform degree of involvement of the caudate and putamen In addition to presynaptic changes in the nigrostriatal neurons, striatal dopamine receptors are altered in Parkinson disease For instance, in early idiopathic Parkinson disease uptake of [11C]raclopride, which is a selective dopamine D2 receptor ligand, increases in the striatum contralateral to the predominant parkinsonian symptoms compared to the uptake in the ipsilateral striatum (129) This up-regulation may disappear to years later (130) A combined FDG and D2 receptor PET study found a positive correlation between striatal glucose metabolic activity and receptor expression in Parkinson disease (131) Studies of the postsynaptic D2 status have demonstrated normal or increased D2 receptor density in early Parkinson disease and decreased receptor density in patients with advanced Parkinson disease or atypical parkinsonism, such as multiple system atrophy and progressive supranuclear palsy Therefore, combined pre- and postsynaptic dopaminergic imaging may distinguish early idiopathic Parkinson disease from atypical parkinsonian disorders (Table 9.1.5) However, combined pre- and postsynaptic dopaminergic imaging may not be able to distinguish atypical parkinsonian disorders from each other or from advanced idiopathic Parkinson disease Dopaminergic PET studies should not be used as a substitute for the clinical diagnosis of Parkinson disease However, neurochemical and functional activation studies may play an important clinical role in the selection of patients with abnormal movements who may benefit from electrical deep brain stimulation Dopaminergic studies may have a limited clinical role in the diagnosis of patients with symptoms suggestive of Parkinson diseases yet not respond to typical anti-Parkinson drugs There is some interest in using dopaminergic PET tracers to aid in the differential diagnosis of essential tremor from early Parkinson disease Dopaminergic Neurochemical Imaging: Differential Diagnosis of Parkinsonian or Lewy Body Dementia from Alzheimer Disease Nigrostriatal dopamine neurons are involved in virtually all patients with parkinsonian dementia, and imaging research studies have demonstrated reduced presynaptic nigrostriatal markers (132,133) Striatal dopaminergic markers are, conversely, normal in Alzheimer disease, and therefore presynaptic dopaminergic imaging can be used for the differential diagnosis between parkinsonian dementia and Alzheimer disease A subset of patients with parkinsonian dementia present clinically with Parkinson disease, followed later by cognitive decline These demented subjects have subtle differences from LWBK053-3787G-9.01[479-499].qxd 14-08-2008 05:56 PM Page 488 Aptara Inc 488 Principles and Practice of PET and PET/CT TA B L E Pre- and Postsynaptic Dopaminergic Activity in Idiopathic Parkinson Disease and Atypical Parkinsonian Disorders Early idiopathic Parkinson disease Advanced Parkinson disease Atypical parkinsonism (e.g., progressive supranuclear palsy or multiple system atrophy) Presynaptic Dopaminergic Nigrostriatal Activity Postsynaptic Striatal Dopamine Receptor Activity T (esp posterior putamen) T T c (up-regulation) normal or T T Parkinson disease in their nigrostriatal dopamine imaging patterns, with relatively symmetrical and diffuse reduction in presynaptic markers in comparison with the side-to-side and putamen-to-caudate nucleus heterogeneity typical of Parkinson disease (Fig 9.1.7) STROKE Current management of patients with acute stroke is centered on CT and MRI CT has traditionally played a prominent role by detecting the presence of hemorrhage However, gradient recalled echo MR may be as accurate as CT for the detection of acute hemorrhage and is also more accurate than CT for the detection of chronic intracerebral hemorrhage (134) MR blood oxygen level-dependent functional imaging is now playing a key role in the very early diagnosis of ischemic stroke (135,136) Multitracer PET imaging has allowed major new insights into the pathophysiology of stroke in humans (137–139) Determinations of CBF, cerebral blood volume (CBV), and cerebral metabolic rate of oxygen (CMRO2) permit the discrimination of various compensatory mechanisms in occlusive vascular disease For example, compensatory changes in the CBF/CBV ratio (indicating a perfusion reserve) and increases in the oxygen extraction fraction (OEF, a marker of metabolic reserve), may prevent ischemic tissue damage during graded flow decreases (138) It has been possible to document the compensatory responses of the brain to reductions in perfusion pressure using PET and to directly relate these responses to prognosis (139) Measurement of Cerebral Oxygen Metabolism, Cerebral Blood Volume, and Oxygen Extraction Fraction Using PET PET measurements of rCBF, cerebral blood volume, oxygen extraction, oxygen and glucose consumption permit a detailed investigation of the pathophysiology of stroke (140) The short-lived PET tracer [15O] (half-life of 123 seconds) was first used to study CBF and cerebral oxygen utilization in man by Ter-Pogossian et al (141,142) Jones et al (143) described a noninvasive inhalational method, using steady state kinetics, to measure the distribution of CBF and OEF in the human brain The continuous inhalation of either molecular [15O] or C15[O2] produces complementary images in that they relate to regional oxygen uptake and blood flow, offering a direct insight to the regional demand-to-supply relationships within the brain (144) The method of quantitative measurement of rCBF and CMRO2 has been described in detail by Frackowiak et al (145) OEF reflects the arterial-venous oxygen difference divided by the arterial oxygen content Reliable OEF estimates can be obtained by combining dynamic C[15O] and [15O2] scans (146) An expression for OEF can be obtained by dividing the cerebral activity obtained during [15O] inhalation by that obtained during C15[O2] inhalation with some additional computations (145) The CMRO2 can be derived from the relationship (145): CMRO2 = CBF ϫ OEF ϫ Total blood oxygen count (from arterial blood sample) Using these methods Frackowiak et al found normal values of CMRO2 of 1.81 Ϯ 0.22 mL O2/100 mL/min in mean white matter and 5.88 Ϯ 0.57 mL O2/100 mL/min in temporal gray matter Corresponding values for CBF were 21.4 Ϯ 1.9 mL /100 mL/min in mean white matter and 65.3 Ϯ 7.0 mL /100 mL/min in mean temporal lobe gray matter (145) Methods other than the steady-state inhalation method have been developed to measure CBF and CMRO2, such as the autoradiographic CBF method using intravenous H2[15O] and newer dynamic methods (147) Cerebral blood volume can be measured by inhalation of C[15O] (148) Quantitative imaging of the OEF has been shown to be of invaluable help in the assessment of the pattern of CBF-CMRO2 coupling (149) Ideally, glucose utilization should be measured simultaneously with CMRO2 in order to provide an accurate assessment of regional energy metabolism Glucose utilization and oxygen use may become uncoupled in acute stroke and this uncoupling may go in two opposite directions, either aerobic glycolysis with relatively increased glucose consumption, or use of substrates for oxidation other than glucose (149) Table 9.1.6 TA B L E Different Pathophysiological Conditions in Stroke Condition CBF CMRO2 OEF Ischemia Oligemia Luxury perfusion low moderately low low/normal/high low normal low very high high low CBF, cerebral blood flow; CMRO2, cerebral metabolic rate of oxygen; OEF, oxygen extraction fraction (From Baron JC, Frackowiak RS, Herholz K, et al Use of PET methods for measurement of cerebral energy metabolism and hemodynamics in cerebrovascular disease J Cereb Blood Flow Metab 1989;9:723–742, with permission.) LWBL053-3787G-IND[713-730].qxd 8/16/08 1:23 AM Page 715 Aptara Inc Index for myocardial oxidative metabolism assessment in hypertrophic cardiomyopathy, 602 for myocardial oxygen consumption assessment, 592–595, 593f, 594f data analysis in, 592–594, 593f experimental studies and method validation in, 594, 594f imaging protocols in, 592 sources of error and limitations of, 594–595 tracer preparation in, 592 for right ventricular oxygen consumption, 601–602 Carbon-11 [11C], 3, 4t, 6–7, 6f as label, 18–20 nuclear reactions and target materials for, 17, 17f physical properties of, 17, 17t production of, 16–18, 17f, 17t production reactions for, properties of, 4t, radioisotope separation for, specific activity of, 4, 4t targetry for, 6–7, 6f time in synthesis of, 16 Carbon-13 [13C], as paramagnetic stable nuclide, Carbon-11 [11C] compounds, 18–20 See also specific compounds Carbon–deuterium bond, 24 Carbonyl-11C-labeled amides, synthesis of, 19 Carbuncle, [18F]-FDG uptake in, 154, 160f Carcinoid heart disease, [68Ga]-DOTANOC/DOTA-TOC receptor PET/CT of, 425 Carcinoid tumor, 411 See also Neuroendocrine tumors Carcinoma of unknown primary (CUP), 438–439 anatomical presentation of, 438–439 categorization of, 438 FDG PET of, 439, 440t, 441f [68Ga]-DOTA-NOC/DOTA-TOC receptor PET/CT of, 427f histologic definition of, 438 literature on PET of, 439, 440t with negative conventional imaging, 441 Cardiac See also Heart entries Cardiac FDG PET imaging protocols, 568 Cardiac metastasis of ileum carcinoid, [68Ga]DOTA-NOC/DOTA-TOC receptor PET/CT of, 426, 427f Cardiac resynchronization for congestive heart failure, 601 PET myocardial perfusion evaluation of, 559 Cardiac stem cell therapy, PET myocardial perfusion evaluation of, 559 Cardiology, pediatric PET and PET/CT in, 447–448 Cardiomyopathy, PET myocardial perfusion evaluation of in dilated cardiomyopathy, 558 in hypertrophic cardiomyopathy, 558 Cardiorespiratory infectious processes, FDG PET/CT of, 629 Cardiovascular disease, hypoxia imaging in, 464–465 Carfentanil, [11C], 29, 30f Carrier added (CA), 18 Carrier free (CF), 17 Cartilage tumors, malignant, 399–400, 399t Castleman’s disease, 267 Catecholamines biosynthesis of, 607–608, 608f radiolabeled analogues of, 609–610, 609f, 610t Catecholamine transport pathway, radiopharmaceuticals based on, 413t, 419 Cation transporters, organic, 667 Cellular proliferation, newer tracers for, 475, 475f Central nervous system tumors classification and grading of, 198 clinical presentation of, 199 diagnosis of, 199 epidemiology of, 198 molecular and genetic alterations in, 198–199 MR imaging of, 199 “noisy” studies on, 204 Central nervous system tumors, PET and PET/CT of, 198–216 for cerebral metastases, 215–216, 215f in children, 450–451, 451f diaschisis, 203 for dysembryoplastic neuroepithelial tumor, 213, 213f for ganglioglioma, 212–213 for gliomatosis cerebri, 213–214 important clinical questions on, 204–212 cell type in, 202f, 206–207, 206f–207f high- vs low-grade tumors in, 202f, 205–206, 205f–207f local practice in, 204–205 malignant degeneration of low-grade glioma in, 207–208, 208f recurrent tumor effects vs treatment effects in, 209–211, 210f, 211f targeting lesion parts in, 207 tumor penetration into surrounding tissue in, 202f, 207f, 208f, 211–212, 211f tumor response to treatment in, 209, 209f medication effects on, 203 PET ligands for imaging brain tumors in, 200–203 carbon-11 methionine and amino acid transport in, 200–201 carbon-11-thymidine and cellular proliferation in, 201 fluorine-11-fluorodeoxyglucose in, 201–203, 202f fluorine-11-fluorothymidine and cellular proliferation in, 201 tumor physiology in, 200 PET ligands for imaging in, 199–200 for pilocytic astrocytoma, 212, 212f for pleomorphic xanthoastrocytoma, 213, 214f for spinal cord tumors, 214–215, 214f technical aspects of PET/CT in brain and, 203–204 Cerebral amyloid angiopathy, PET amyloid imaging of, 698 Cerebral blood flow (CBF), 480–483 diaschisis on, 483, 483f factors affecting, 482, 482f imaging of, 480 interictal H2[15O] PET studies of, 493 in movement disorders, 483, 484t normal aging on adulthood to elderly, 482 infancy to adulthood, 481–482 normal variants of, 481, 481f, 481t in stroke, 488–489, 488t, 489t Cerebral metastases, 215–216, 215f Cerebral oxygen metabolism, in stroke, 488, 488t Cervical cancer epidemiology of, 348 FDG PET as surrogate marker for drug treatment benefit in, 709 patient preperation and imaging of, 348 prognosis with, 349–350 staging of, 348–349 cervical cancer, FDG/in PET for directing therapy, 350–351, 351f–352f for posttherapy monitoring 351–352, 353f for prognosis analysis, 349–350 of staging, 349 CGP12177, 11C, for postsynaptic receptor imaging, 610 715 Chemical microspheres, 663f–665f, 664–666 copper-PTSM, 666 nitrogen-13-ammonia, 666 rubidium-82 chloride, 663f–665f, 664–666 Chemistry, radiotracer See Radiotracer/tracer chemistry; specific radiotracers Chest, normal [18F]-FDG uptake in, 139, 140f Chest CT, for pulmonary nodule detection, 136 Chiral molecules, biological targets as, 23 Cholangiocarcinomas, 339, 341–343, 342f, 343f See also Hepatobiliary tumors Cholecystokinin (CCK), radiopharmaceuticals based on, 420, 420t Choline, [11C], 474 Choline, [11C], PET and CT, image fusion in, 112–113, 113f Choline acetyltransferase (ChAT), 607, 608 Cholinergic system, radiotracers for, 31–33, 32f, 33f acetylcholinesterase, 31–32, 32f muscarinic cholinergic receptor, 31, 32f nicotinic acetylcholine receptor, 32–33, 33f Chondrosarcomas, 399–400, 399t Chorea, 486 Choreiform movement disorders, 486 Chromatographic nuclide generator systems, 9–10 Chronic arterial occlusive disease, hemodynamic reserve and, 489–490 Cigarette smoking molecular imaging of, 528–529 PET myocardial perfusion evaluation of, 557 Clorgylein, [11C], 27, 28f Clusters of differentiation, in malignant lymphoma, 267 CNS5161, [11C], 36f, 37 Cocaine, [11C], 26, 27f Cocaine abuse, molecular imaging of, 526–527 Cocaine craving, cue-induced, 527 Cognitive function, PET and PET/CT mapping of, 493 Coincidence detection, 48, 48f Coincidence events, 48 delayed, 79 scattered, 79–80 Coincidence resolving time, 78 Coincidences multiple, 78–79, 79f random, 78–79, 79f Coincidence window, 78 Col-3, 679 Colon polyp, [18F]-FDG uptake in, 147f, 148 Colony stimulating factors, bone marrow [18F]FDG uptake from, 151, 156f Colorectal carcinoma, epidemiology of, 320 Colorectal carcinoma, PET and PET/CT of, 320–328 cost and reimbursement issues with, 327 limitations of FDG in, 327 metastases of [18F]-FDG uptake in, 147f, 148 hepatic, 133f new tracers in, 327–328 recurrent or metastatic, detection of, 322–327 ASCO recommendations for, 322–323 clinical impact of PET/CT in, 327 conventional modalities in, 323 cost analysis for, 326–327 FDG PET in, 323–324, 324f–325f FDG PET in monitoring therapy in, 325–326 FDG PET on patient management in, 324–325 for screening and diagnosis, 320–321, 321f for staging, initial, 321–322, 322f as surrogate marker for drug treatment benefit in, 708 LWBL053-3787G-IND[713-730].qxd 8/16/08 1:23 AM Page 716 Aptara Inc 716 Index Combretastatin, 680 Compartmental impulse response functions, 666 Compartmental modeling, 83–98 data acquisition considerations for, 92–95 blood-borne radioactivity, 95 measuring radiotracer concentration in arterial plasma, 92–94, 93f design and implementation steps for, 84–87, 84f defining dynamic process to be measured, 84 defining measured quantities and unknown parameters, 85 developing mathematical schemes for estimating model parameters, 86–87 developing workable compartmental model, 84, 84f model validation, 87 practical considerations, 87 selecting appropriate radiotracer, 84 sensitivity analysis/model optimization, 87 understanding biological significance of model parameters, 85–86 understanding model assumptions, 85 understanding radiotracer physiology and biochemistry, 84 writing/solving equations on tracer exchange between model compartments, 85 fundamentals of, 83–84, 83f model complexity and trade-off in bias vs precision in, 91 model validation in, 97–98, 98f, 99f parameter estimation in, 95–97 nonlinear regression techniques, 95–96, 96f specialized graphical approaches, 96–97 use of, 95 without arterial input functions, 97 for pharmacological studies, 91–92, 91f for tracer models with multiple tissue compartments, 87–91 for [18F]-FDG, 89–91, 90f overview of, 87–88 volumes of distribution for multicompartment models in, 88–89, 88f Compound nucleus Bohr’s model of, 1–2 formation and disintegration of, 2, 2f Compton scattering, 79–80 Computational load, reduction in, 74 Computed tomography (CT) See CT (computed tomography) Computed tomography angiography (CTA), of renal artery stenosis, 661 Computed tomography-magnetic resonance imaging (CT-MRI), of neuroendocrine tumors, 421 Conduct disorder, 526 Congestive heart failure acipomox for, 601 beta-adrenergic drugs for, 599, 600f calcium sensitizers for, 600–601, 600f drug therapy evaluation in, 599–601, 600f levosimendan for, 600–601, 600f mechanical therapy evaluation in cardiac resynchronization, 601 continuous positive airway pressure, 601, 602f metabolic modulators for, 601 myocardial efficiency with, 599–601 myocardial neurotransmitter imaging of, 615 Continuous positive airway pressure (CPAP), for congestive heart failure, 601, 602f Contrast agents, CT adverse reactions to, 133 on attenuation-corrected PET data, 133, 134f for PET/CT, 131–133, 135 IV, 132–133, 132f, 133f oral, 131–132, 132f on tracer quantification, 133 water-equivalent oral, 131–132, 132f Copper-61 (61Cu), Copper-64 (64Cu), 8–9 Copper complexes, for hypoxia imaging, 466–467 Coregistration of 3-D data sets, 98–102 intersubject registration, 102 intrasubject, intermodality registration, 100–102, 101f, 102f intrasubject, intramodality registration, 100 overview, 98–100 Coronary artery disease, 565 heart failure from, 565 hypertension as risk for, 598–599 myocardial perfusion in, 541–559 (See also Myocardial perfusion evaluation, PET) PET myocardial perfusion evaluation of for diagnosis, 552, 553t, 554f, 554t for myocardial blood flow reserve assessment, 556 for prognosis, 552, 554f, 555t Coronary artery disease assessment, carbon-11acetate in, 597–598, 598f Coronary flow reserve, PET myocardial perfusion evaluation of, 549, 550f, 550t, 556 Coronary viability assessment, carbon-11-acetate in, 597–598, 598f Corticobasal degeneration, 485–486, 486f pre- and postsynaptic dopaminergic neurochemical imaging of, 487, 487t Crohn’s disease, FDG PET/CT of, 627–629, 628f Crossed cerebellar diaschisis (CCD), 203 Cross section, CT (computed tomography), in PET/CT, 58–68 See also PET/CT advantages of, 58 CT scanners in, 60 CT scan protocol in, with [18F]-FDG, 125–126 fundamentals of CT in, 59–60 fundamentals of PET/CT and, 58–59, 59f future developments in, 67–68 image artifacts in, 66–67, 66f, 67f multiple-row detector CT (MDCT) in, 60 multiple-row detector design arrays in, 60–63, 61f–62f pitch in, 63, 64f quality control and shielding requirements in, 65 radiation dose in, 65–66, 65t scan parameters/protocols in, 59, 63–64, 63f, 64t transmission scans with germanium rods in, 64–65 utilization of, 58 CT (computed tomography), of children, 444–445, 445t CT attenuation curves (CTACs), 52, 54f CT gantry, 60 CT-MRI (computed tomography-magnetic resonance imaging), of neuroendocrine tumors, 421 CT number, 60 CT optimization for PET/CT, 131–137 CT contrast agents in, 131–133 on attenuation-corrected PET data, 133, 134f IV, 132–133, 132f, 133f oral, 131–132, 132f CT protocols in for therapy assessment, 137 for tumor staging, 134–137, 136f chest CT for pulmonary nodule detection in, 136 contrast agents in, 135 CT acquisition parameters in, 135 field of view in, 134–135 patient positioning in, 135 radiation issues in, 137 respiration issues in, 136f, 137 CT scanners, 60 Cu-ATSM, for hypoxia imaging, 466–467 Cue-induced cocaine craving, 527 Cyclotrons, “small,” Cytosine deaminase, 645, 646t D Data acquisition system (DAS) channels, 60, 61f Data corrections, in image processing, 77–83 attenuation in, 80–82, 80f, 81f detector dead time in, 78 gating in, 82–83 normalization in, 77–78 random and multiple coincidences in, 78–79, 79f scattered coincidence events in, 79–80 Dead time, detector, 78 Decay, positron, 47, 48t Decay characteristics, of PET radionuclides, 4, 4t Deconvolution methods, 88 Degenerative joint disease, [18F]-FDG uptake in, 143 Degrading factors, 50–52, 51f Degrees of freedom (DOF), geometric, 112 Delayed coincidence events, 79 Dementia classification of, 500–501, 501t epidemiology of, 500 MRI imaging for evaluation of, 506, 506f SPECT imaging of, 501t, 502, 505 Dementia, FDG PET imaging of, 500–513 for clinical work-up, 500–501, 501t cost-benefits of, for dementia work-up, 512–513 for diagnosis, 501, 501t FDG, 501t, 502 frontal hypometabolism in, 511, 512t history of, 500 for metabolic patterns, 506–512, 506f of Alzheimer disease, 507–508, 507f–509f of dementia with Lewy bodies, 510–512, 512f of frontotemporal dementia, 509–510, 509t, 510f, 511f of mild cognitive impairment, 508–509, 509f, 513f of Parkinson disease with dementia, 510–511 non-FDG radiotracers for dementia in, 505 PET vs PET/CT in, 502–505 brain FDG PET imaging protocols in, 502 FDG PET imaging interpretation in, 502–504, 503f–505f, 504t pixel normalization in, 504–505 quantification in, 504 statistical mapping in, 505, 505f Z-score maps in, 509, 513f Dementia with Lewy bodies, 484, 485t dopaminergic neurochemical imaging for diagnosis of, 487–488, 487f metabolic patterns of, 510–512, 512f PET amyloid imaging of, 697, 697f Density, organ, in Hounsfield (H) units, 131, 132f Dental artifact, 234, 235f Dental implant, artifacts from, 234, 235f Dentarubropallidoluysian atrophy, 486 2-Deoxy-D-glucose, chemical structure of, 22f 2-Deoxy-2-[18F]-fluoro-D-glucose (18FDG) See Fluorodeoxyglucose ([18F]-FDG) 2-Deoxy-glucose, positron emitter labeled version of, 21–22, 22f LWBL053-3787G-IND[713-730].qxd 8/16/08 1:23 AM Page 717 Aptara Inc Index L-Deprenyl-D2, [11C], 27, 28f Depression, SPECT and PET of, major depressive disorder, 520–523, 522f Detector dead time, 78 Detectors, radiation, 49, 50f Deuterium, isotope effects of, 24, 24f Diabetes mellitus (DM) myocardial neurotransmitter imaging of, 613–614, 613f PET myocardial perfusion evaluation of, 557 1,2-Diacylglycerol, [11C], 34, 34f Diaphragm, [18F]-FDG distribution in, 141, 142f Diaschisis, 203, 483, 483f, 490 Differentiation clusters, in malignant lymphoma, 267 Digital subtraction angiography (DSA), of renal artery stenosis, 661 Dihydrotetrabenazine, [11C] ([11C]DTBZ), 27, 27f Dihydroxyphenylalanine [11C], for neuroendocrine tumors, 431–433, 433f [18F], for neuroendocrine tumors, 431–433, 433f Dihydroxyphenylalanine decarboxylase in cocaine abusers, 527 striatal activity of, 517 Dilated cardiomyopathy, PET myocardial perfusion evaluation of, 558 Diprenorphine, [11C], 29–30, 30f DNA mutations, in cancer, 117 DNA synthesis as PET target for drug development, 637 radiotracers for, 35, 35f Dobutamine stress test, PET myocardial perfusion evaluation of, 545 Dopamine baseline striatal activity of, 518, 518f endogenous synthesis of, 25 metabolism of, 23f, 25 nicotine on, 529 reuptake of, 25 roles of, 25 stimulant-induced release of, 526–527 vesicular transporters and, 26–27, 27f Dopamine D1 receptor, 25 Dopamine D2 receptor, 25 in addiction, 526f in alcohol abuse, 526f, 529 in cocaine abuse, 526f extrastriatal, 519 as PET target for drug development, 637, 638f Dopamine D3 receptor, 25, 26 Dopamine D4 receptor, 25, 26 Dopamine D1 receptor antagonists, 26 Dopamine nerve terminal, nigrostriatal, 486, 487f Dopamine receptors, 25–26 See also specific receptors prefrontal, 519 radioligands for, 25, 26f reuptake by, 25 striatal, 517 subtypes of, 25 Dopaminergic neurochemical imaging, 486–487, 487f for parkinsonian disorders, pre- and postsynaptic, 487, 487t for parkinsonian or Lewy body dementia, differential diagnosis of, 487–488, 487f Dopamine system, brain, radiotracers for, 25–28 dopamine and vesicular transporters in, 26–27, 27f dopamine metabolism in, 23f, 25 dopamine receptors in, 25–26, 26f monoamine oxidase in, 27–28, 28f Dopamine transmission in alcoholism, 529 in cocaine abuse, 526–527, 526f in major depressive disorder, 523 in personality disorders, 525 in schizophrenia, 517–519, 518f prefrontal, 519 subcortical, 517–519, 518f in social phobia, 525 Dopamine transporter (DAT) in cocaine abuse, 527 in ecstasy abuse, 528 in methamphetamine abuse, 527–528 striatal, 518–519 Dosimetry, radiation, in children, 444–445, 444t, 445t DOTA, [68Ga], 420–421 DOTA-NOC, [68Ga], 420, 424–425 DOTA-NOC/DOTA-TOC receptor PET/CT, [68Ga], 422–431, 423f–431f of carcinoid heart disease (Hedinger syndrome), 425 of cardiac metastasis of ileum carcinoid, 426, 427f clinical results of, 426–431, 427f–432f in bone lesions, 426, 428f diagnostic efficiency of, 429, 429f, 431, 432f in small cell lung cancer, 429, 432f in tumor lesions, 426, 427f in upper abdominal metastases, 426, 429 of gastrinoma, 423f–424f of glomus tumor, 425f of liver metastasis of pancreatic neuroendocrine tumor, 429, 432f of meningioma, 426f of neuroendocrine carcinoma of small bowel with metastases, 429f of pancreatic neuroendocrine tumor, local recurrence of, 431f patient preparation, imaging, and reporting in, 422–424, 427f of pheochromocytoma/paraganglioma, 426, 428f of retro-orbital metastasis of neuroendocrine carcinoma (CUP syndrome), 427f of thyroid cancer, 430f tumor response to treatment criteria in, 422, 422t DOTA-TATE, [68Ga], 420 DOTA-TOC, [68Ga], 420–421, 424–425 Drug delivery assessment, PET, 635–636 of anti-infective drugs (target penetration), 635–636, 635f of delivery to tumor, 636, 636f Drug development, 634 Drug development, PET in, 634–642 cellular and molecular targets for, 636–641, 637t categories, 636, 637t desirable probe characteristics, 637, 637t DNA synthesis rate, 637 estrogen-receptor blockage by tamoxifen, 638–639, 638f FDG as probe, 636 monoamine oxidase B enzyme inhibition, 640–641, 640t, 641f, 642f neuroreceptors D2 and 5-HT2, 637, 638f receptors and enzymes, 637 tumor cell proliferation probed with thymidine analogues, 639, 639f, 640f drug delivery assessment in, 635–636 of anti-infective drugs (target penetration), 635–636, 635f of delivery to tumor, 636, 636f efficacy issues in, 640, 640t hypothesis testing stages in, 641, 641t 717 imaging information and therapeutic hypothesis in, 637–638 overview of, 634–635, 635t Drug development, question-based, 634, 635t Drug occupancy studies of antidepressants in major depressive disorder, 523, 524f of antipsychotics for schizophrenia, 519–520 Dynamic contrast enhanced MRI (DCE MRI), neovasculature imaging with, 677, 679–680 Dysembryoplastic neuroepithelial tumor, 213, 213f E Early onset familial Alzheimer disease (eoFAD), 690, 698–699, 698f See also Amyloid imaging Early response assessment, 261 Ecstasy abuse, SPECT and PET of, 528 Effective glycolytic volume (EGV), 108 Effective specific activity, 18 Efficacy in drug development, PET assessment of, 640, 640t Embryonal rhabdomyosarcoma, pediatric PET and PET/CT for, 450f EMD-121974, 678 Enantiomers, active vs inactive, 23–24 Endoergic reaction, Endometrial cancer, 352–353 Endometrium, at menstrual ovulation, [18F]-FDG uptake in, 149, 159f Endothelial cell proliferation inhibitors, 678 Endothelial cell signal transduction inhibitors, 678 Endothelial dysfunction, with coronary risk factors, PET myocardial perfusion evaluation of, 558 Endothelial function, PET myocardial perfusion evaluation of, 549–550, 551t Energy metabolism, glucose oxidation in, 480 Enriched targets, in PET radionuclide production, Enzymes, as targets for PET drug development, 637 Epilepsy in childhood, epidemiology of, 445 classification of, 491 Epilepsy, PET and PET/CT of, 491–494 for benzodiazepine neuroreceptor imaging, 494 for extratemporal lobe epilepsy, 492, 492f glucose metabolic PET studies in of infantile spasms, 492–493 of Lennox-Gastaut syndrome, 493 ictal PET in, 493, 493f interictal H2[15O] cerebral blood flow studies in, 493 in management, 491 mapping cognitive and language functions in, 493 pediatric, 445–447, 446f for regional glucose hypometabolism in interictal expression of epileptogenic foci, 491 in temporal lobe epilepsy, 491–492, 492f for serotonin synthesis imaging, 494 Epinephrine, [11C], for neuroendocrine tumors, 434 EP2140R, 680 ERK mitogen-activated protein kinase (MAPK), 464 LWBL053-3787G-IND[713-730].qxd 8/16/08 1:23 AM Page 718 Aptara Inc 718 Index Esophageal carcinoma classification of, 310 epidemiology of, 310 FDG PET as surrogate marker for drug treatment benefit in, 708 management changes for, 317 spread of, 310 survival with, 310 treatment of, 310 Esophageal carcinoma, PET and PET/CT of, 311–317 cost-effectiveness of, 317 for detection, primary tumor, 311–312 locoregional nodal detection in, 312, 312t other PET tracers in, 317 PET/CT in, 316 for radiation therapy planning, 194 for radiation treatment planning, 316–317 for recurrent disease detection, 313 reimbursement for, 317 for staging, 310, 311t, 314f for systemic metastases, 312–313, 313t for therapy response assessment, 313–316, 315t, 316f for tumor response, 311 Esophagitis, [18F]-FDG uptake in, 145, 146f Esophagus, [18F]-FDG distribution in, 143–144, 146f Essential tremor, 486 Estrogen receptors in breast cancer, 118 tamoxifen blockage of, as PET target for drug development, 638–639, 638f Ethylenediaminetetraacetic acid (EDTA), as glomerular filtration tracer, 663f, 666 Ewing sarcoma in children, PET of, 454–455, 456f Ewing’s tumors, 398–399, 398t Excitation energy, 1–2 Excited nucleus, Exercise stress, PET myocardial perfusion evaluation of, 545–546 Exercise training, PET myocardial perfusion evaluation of, 557 Exoergic reaction, Expiration hold, in PET/CT, 136f, 137 Expression substrate, 661–662 Extra-domain B of fibronectin (EDB), imaging of, 686 F Fallypride, [18F], in antipsychotic drug occupancy studies, 520 False-positives, in pediatric PET and PET/CT, 448–449 Farnesyl transferase inhibitors (FTIs), 669 Fasting, before PET and PET/CT, 107 Fatty acid oxidation, 590, 590f FAZA, [18F], for hypoxia imaging in oncology, 466, 467–468, 468f, 469f, 476, 476f FBT, [18F], 32, 32f FDAG, [11C], 34, 34f FDDNP, [18F], 35, 35f FDG-labeled leukocytes, for infection and inflammation imaging, 629 FDG 6-phosphate, 119 18 FETA, [ F], for hypoxia imaging, 466 FETNIM, [18F], for hypoxia imaging, 466 Fever of unknown origin (FUO), FDG PET/CT of, 622–624, 624f Fibronectin, imaging of extra-domain B of, 686 Field of view, for PET/CT, 135 Filtered back-projection (FBP) in reconstruction algorithms, 71–73, 72f, 73f with reprojection, for 3-D PET, 75 Fine-needle aspiration, of thyroid cancer, 243–245 FLT, [18F], 35, 35f Fluorine-18 [18F], 3, 5–6 See also specific radiotracers and compounds compounds labeled with, 20–21, 20f in newer tracers for cancer imaging, 472–473 nuclear reactions and target materials for, 17, 17f physical properties of, 17, 17t production of, 16–18, 17f, 17t production reactions for, properties of, 4t, radioisotope separation for, targetry for, 5–6, 6f Fluoro-A-85380 2-[18F], 33, 33f 6-[18F], 33, 33f Fluoro-A85830, 6-[18F], 21 Fluorobenzyl triphenyl phosphonium, [18F], as myocardial blood flow tracer, 542t, 543f, 544 Fluorocholine (FCH), [18F], for cancer imaging, 474, 474f Fluorodeoxyglucose ([18F]-FDG), 5, 20, 20f See also specific disorders availability of, 634 in brain, 22, 22f for cardiac imaging, 121–122 compartmental model for, 89–91, 90f for dementia, brain imaging with, 501t, 502 distribution of, in children, 448, 449f image artifact from, 67, 67f in infection and inflammation, mechanism of uptake of, 619–620 kinetic modeling of, 118, 118f limitations of, 121 for neuroendocrine tumors, 433–434 in pediatrics, 444–445, 444t tumor response monitoring with, 170–171 Fluorodeoxyglucose ([18F]-FDG) cancer imaging, 117–128 See also specific cancers chemotherapy on, 121 cost-effectiveness of, 127 fusion of form and function in, 126–127, 126f, 127f glucose metabolism as target in, 118–119, 118f historical perspective on, 117 imaging device in, 122 vs inflammation and infection, 121 injection and imaging in, 124–126 in lung cancer, 120, 120f molecular and functional alterations in cancer and, 117–118, 118t patient selection for PET in, 123 practical issues of PET in, 122 protocol choice for CT scan in, 125–126 quantitative measurements in, 126 understanding [18F]-FDG PET signal in, 119–122, 119f, 120f, 121t Fluorodeoxyglucose ([18F]-FDG) distribution, normal variant, 140–153 alimentary tract, 143–148, 146f–148f bone marrow, 150–151, 154f–156f bowel, 144–147, 147f–148f brown adipose tissue, 142–143, 144f–145f esophagus, 143–144, 146f forearm muscle, 140f, 141 genitourinary tract, 149, 149f–152f laryngeal and vocalization muscles, 141, 143f lymphoid tissue, 140f, 151–153, 156f–157f myocardium, 140, 141f ovaries, 149, 152f palatine tonsils, 153, 157f respiratory muscles and diaphragm, 141, 142f skeletal muscle, 140f, 141–142, 142f–144f stomach, 144, 147f testicles, 149, 152f thyroid, 149, 149f, 153f tongue, 141–142, 144f truncal muscles, 141, 142f uterus, 149, 151f Fluorodeoxyglucose ([18F]-FDG) distribution, whole-body, 139, 140f Fluorodeoxyglucose ([18F]-FDG) uptake in cancer, 106–107, 119–120, 119f, 120f, 121t in gene therapy assessment, 647–648, 647f in glucose metabolism assessment, 647, 647f Fluorodeoxyglucose ([18F]-FDG) uptake, nonmalignant tumor, 153–154, 158f atherosclerosis, 154, 160f benign adrenal hypertrophy and adenoma, 153, 158f cutaneous carbuncle, 154, 160f degenerative/inflammatory joint disease, 143 gynecomastia, 153, 158f healing fractures, 154, 162f inflammation-related, 154, 159f–166f, 163, 165 lymph nodes, inflammatory response, 165, 165f–166f myositis ossificans, 153–154, 158f occupational lung disease, 164–165, 165f pancreatitis, 154, 162f percutaneous tube insertion, 154, 159f pleurodesis, 154, 161f pyogenic infection, 154, 161f radiation pneumonitis, 163, 164f radiation therapy sequela, 163, 163f, 164f sacral insufficiency fracture, 154, 163f sarcoidosis, 163, 164f vascular grafts, 154, 160f vertebral fracture, 154, 155f Warthin tumors of parotid gland, 154, 159f wound healing, 154, 159f Fluorodopa, 6-[18F], 23f, 25 Fluorodopamine, [18F], 21 for PET imaging of neuroendocrine tumors, 431–433, 433f for presynaptic function imaging, 609f, 610 Fluoroestradiol, 6-[18F], 21 Fluoroethoxybenzovesamicol, [18F], for presynaptic function imaging, 610 Fluoroethyl-L-tyrosine, [18F] (FET), for cancer imaging, 473, 473f Fluoronorepinephrine, [18F], 21, 610 5-Fluorouridine, [18F], 35, 35f FMISO, [18F] for hypoxia imaging, 466 for hypoxia imaging in oncology, 467–469, 468f, 469f Focal soft tissue infections, FDG PET/CT of, 624–625 Forearm muscle, [18F]-FDG distribution in, 140f, 141 Foreign body inflammatory reaction, focal, 629 Forskolin, [11C], 34, 34f Fourier rebinning (FORE), for 3-D PET, 76 Fourier transform, 72–73 FP-TZTP, [18F], 31, 32f Fractures, healing, [18F]-FDG uptake in, 154, 162f Free fatty acids (FFAs), 590 Freely diffusible tracers, renal, 662–664, 663f, 664b Frequency space, 72 Frequency-space filter, 72 Frontal hypometabolism, differential diagnosis of, 511, 512t LWBL053-3787G-IND[713-730].qxd 8/16/08 1:23 AM Page 719 Aptara Inc Index Frontotemporal dementia, metabolic patterns of, 509–510, 509t, 510f, 511f Frontotemporal lobal degeneration, PET amyloid imaging of, 697–698, 697f Functional brain imaging, 479–480 Functional coupling, 480 Functional genomics, 655 Functional imaging, with PET, 634–635 Fusion, image See Image fusion G GABAA receptor, benzodiazepine binding on, 30 GABAergic function, in alcoholism, 529–530 Gadolinium, nephrogenic systemic fibrosis from, 581 Galacto-RGD, [18F], for imaging ␣3 expression, 681–682, 683f Gallbladder carcinoma, 339, 341, 342f See also Hepatobiliary tumors Gallium-68 [68Ga], 420 for imaging blood volume, 680 in newer tracers for cancer imaging, 473 for PET/CT of infection and inflammation, 630 production routes for, Gallium-68 [68Ga] labeling of DOTA-NOC, 420 of DOTA-TATE, 420 of DOTA-TOC, 420–421 of peptides, for PET/CT of infection and inflammation, 630 Gamma camera imaging, 2-D nature of, 69–70 ␥-aminobutyric acid secretion transmission, in schizophrenia, 519 Ganglioglioma, 212–213 Gastrinoma, [68Ga]-DOTA-NOC/DOTA-TOC receptor PET/CT of, 423f–424f Gastrin-releasing peptide receptors, radiopharmaceuticals based on, 419, 420t Gastroenteropancreatic (GEP) tumor See Neuroendocrine tumors Gastrointestinal cancer, PET treatment response monitoring with, 181–183, 182f, 183t Gastrointestinal stromal tumors (GISTs), 402–408 CT and MRI of, initial, 403 epidemiology of, 402 FDG PET/CT of, 407 FDG PET of for initial evaluation, 403–406, 403f–405f for monitoring therapeutic response, 406–408 for patient follow-up, 406–408 historical perspective on, 402 of jejunum, 132f metastases of, 402 treatment of, 402–403 Gated FDG PET imaging, of myocardial viability, 575, 575f Gating, 82–83 GBR13119, [18F], 26, 27f Gene expression, imaging, 644–656 of antisense oligonucleotides, 655–656 of gene transfer, 644, 645t of iodide uptake in malignant tumors, enhancement of, 652–655, 653f for monitoring gene therapy via therapeutic effects, 646–648, 647f with nonsuicide reporter genes, 649–650, 649f of protein–protein interaction, 650–652, 651f of suicide gene activity via specific substrate uptake, 648–649 of suicide gene therapy, 645, 646t of viral vector biodistribution, 644–645 Generalized anxiety disorder, 524 Generator equations, for PET radionuclides, 10–11 Generator-produced positron-emitting radionuclides, PET, 9–10, 9t See also specific radionuclides Generator systems chromatographic nuclide, 9–10 radionuclide, 9–10 Genes, in cancer, 474–475 Gene silencing, 655 Gene therapy monitoring of, via measurement of therapeutic effects, 646–648, 647f for renal disease, 672 Gene transfer, imaging, 644, 645t Genitourinary malignancies, epidemiology of, 366 Genitourinary malignancies, PET and PET/CT of, 366–386 See also specific malignancies for androgen receptor imaging, 371–372 for bladder cancer, 380–385 carbon-11 acetate in, 368–369, 370t challenges of, 372 choline in, 369–371, 370t FDG in, 366–368, 368f, 370t glucose consumption in cancer and, 366–367 HIF in, 368 methionine in, 369, 370t for prostate cancer, 372–379 for renal cancer, 379, 380f, 381f for testicular cancer, 385–386, 386t for treatment response monitoring, 183–184 for tumor proliferation, 372 Genitourinary tract, [18F]-FDG distribution in, 149, 149f–152f Genome, altered, in cancer, 117 Geometric degrees of freedom, 112 Germanium-68/gallium-68 generator, 420 Germanium rods, transmission scans with, 64–65 Gilles de la Tourette syndrome, 525 Glioma, in children, PET of, 450–451, 451f Gliomatosis cerebri, 213–214 Glomerular filtration, tracers for, 666 Glomus tumor, [68Ga]-DOTA-NOC/DOTA-TOC receptor PET/CT of, 425f Gluc-Lys ([18F])-FP-TOCA PET, for neuroendocrine tumors, 433 Glucose in cancer, mechanisms of, 366–367 chemical structure of, 22f Glucose metabolism, 565 in cancer, 106–107 (See also specific cancers) factors affecting sudies of, 482, 482f [18F]-FDG imaging of, 118, 118f (See also specific disorders) in ischemic myocardium, 565 oncogenic transformation on, 119 radiopharmaceuticals based on, 419 in thyroid, 240–241 Glucose oxidation, 480, 590, 590f Glucose transporters (GLUTs), 119, 565, 668 overexpression of, in cancer, 119–120, 120f, 367 renal, 668 Glucose utilization, in cancer, 119–120, 119f Glutamate receptor, metabotropic (mGluR), radiotracers for, 36f, 37 Glutamate receptors, metabotropic (mGluR), 37 Glutamate system, brain, radiotracers for, 36f, 37 Glycolysis, aerobic, 366–367 Glycolytic metabolism, tumor growth via, 119 Growth factor antagonists, 678 Growth plate uptake, of FDG, 448, 449f GVG ([carboxyl-11C]-␥-vinyl-␥-amino-butyric acid), [11C], synthesis of, 19 Gynecological tumors, PET and PET/CT of See Cervical cancer; Uterine cancer; Specific types 719 cervical cancer, 348–352, (See also Cervical cancer) endometrial cancer, 352–353 Gynecomastia, [18F]-FDG uptake in, 153, 158f H Half-life, radionuclide, 47, 48t Hashimoto thyroiditis, [18F]-FDG uptake in, 149, 153f Head and neck cancer, PET and PET/CT of, 221–236 advanced cross-sectional imaging in, 226 conventional imaging in, 223, 226 for evaluation, 226–231 general points on, 226 for prognosis, 230 for staging, 227–228, 228f, 229f for surveillance and staging, 229–230, 229f, 230f for treatment complications, 230–231, 231f for treatment planning, 228–229 for unknown primaries, 226–227, 227f evaluation protocols in, 221–222 FDG PET as surrogate marker for drug treatment benefit in, 708–709 physiologic FDG distribution in, 222–223, 222f–225f pitfalls of, 231–236 artifacts in, 234–236, 235f, 236f atypical and altered physiologic structures in, 231–234, 233f for radiation therapy planning, 192f, 193–194, 193f for salivary gland malignancies, 231, 232f for treatment response monitoring, 176–178, 176t, 177f Healing fractures, [18F]-FDG uptake in, 154, 162f Heart See also Cardiac entries autonomic nervous system in, 607–608, 608f Heart disease, carcinoid, [68Ga]-DOTANOC/DOTA-TOC receptor PET/CT of, 425 Heart disease, nonatherosclerotic, PET myocardial perfusion evaluation of, 558–559 dilated cardiomyopathy, 558 heart transplant, 558 hypertrophic cardiomyopathy, 558 pediatrics, 546f, 558–559 syndrome X, 558 valvular heart disease, 558 Heart failure, 565 Heart innervation, 607 Heart transplantation PET myocardial perfusion evaluation of, 558 reinnervation after, myocardial neurotransmitter imaging of, 614–615, 614f Hedinger syndrome, [68Ga]-DOTA-NOC/DOTATOC receptor PET/CT of, 425 Helical CT, 60 Hematopoietic stimulating factors, on FDG uptake, 449, 450f Hematopoietic stimulation, bone marrow [18F]FDG uptake from, 151, 156f Hemodynamic reserve, chronic arterial occlusive disease and, 489–490 Hemorrhagic infarction, pediatric PET and PET/CT for, 447 Hemorrhagic stroke, PET and PET/CT of, 490 Hepatic metastases, from colorectal cancer, 133f Hepatobiliary tumors biopsy of, 339 CT of, 339 epidemiology of, 338–339 LWBL053-3787G-IND[713-730].qxd 8/16/08 1:23 AM Page 720 Aptara Inc 720 Index Hepatobiliary tumors (Continued) magnetic resonance cholangiopancreatography of, 339 MRI of, 339–340 retrograde cholangiopancreatography of, 339 screening of, 339 ultrasound of, 339 Hepatobiliary tumors, PET and PET/CT of, 338–344 carbon-11-acetate in, 341, 342f for cholangiocarcinomas, 339 dual-tracer PET for evaluation in, 341 FDG PET in for cholangiocarcinoma, 341–343, 342f, 343f for detecting recurrences, 341 for diagnosis, 340–341, 340f for gallbladder carcinoma, 341, 342f monitoring therapy in, 341 for primary sclerosing cholangitis, 341 for staging, 341 for gallbladder carcinoma, 339 for hepatocellular carcinoma, 339 Hepatocellular carcinoma, 339 See also Hepatobiliary tumors Hepatocyte growth factor (HGF), 672 Hepatocyte growth factor (HGF) gene transfer, 672 Heroin abuse, SPECT and PET of, 528 Hibernating myocardium, 565–567, 566f, 567t, 568f High- vs low-grade tumors, of central nervous system, 202f, 205–206, 205f–207f hNET gene transfection, 654–655 Hodgkin’s lymphoma in children, PET of, 451–452, 451f Hot atom, 3–4 Hot atom chemistry and radiolysis, 3–4, 16–17 “Hot spot” artifacts, 167, 167f Hounsfield units, 60 Hounsfield (H) units, in organ density, 131, 132f 5-HT2, as target for PET drug development, 637, 638f 5-HT1A receptors in major depressive disorder, 521 radiotracers for, 29 in schizophrenia, 519 5-HT2A receptors in obsessive compulsive disorder, 525 radiotracers for, 28–29, 28f in schizophrenia, 519 5-HT2 receptors, in major depressive disorder, 520–521 Human immunodeficiency virus (HIV) infection, FDG PET/CT of infection in, 626–627 Human norepinephrine transporter (hNET), 654 Huntington disease, 486 Hurthle cell carcinoma, 245 Hydroxyepiphedrine, [11C], for neuroendocrine tumors, 434 5-Hydroxytryptamine (HTP) PET, [11C], for neuroendocrine tumors, 433 Hypercalcemia, bone disease and, 268 Hyperemic myocardial blood flow, PET myocardial perfusion evaluation of, 549, 550f, 550t Hyperinsulinemia, 18F-fluorodopa PET of, 433, 433f Hyperlipidemia, PET myocardial perfusion evaluation of, 556–557 Hypertension in coronary artery disease, 598–599 myocardial efficiency with, 598–599 PET myocardial perfusion evaluation of, 557–558 Hypertrophic cardiomyopathy myocardial oxidative metabolism in, 602 PET myocardial perfusion evaluation of, 558 Hypothesis, therapeutic, imaging information and, 637–638 Hypothesis testing stages, 641, 641t Hypoxia, 464 Hypoxia imaging, 464–469 after stroke, 491 in cardiovascular disease, 464–465 measurement challenges in, 465–466 newer tracers for, 476, 476f in oncology, 465, 465f, 467–469, 468f, 469f PET radiopharmaceuticals for copper complexes, 466–467 nitroimidazole compounds, 466 Hypoxia-inducible factors (HIF-1␣, HIF-2␣), 119, 120, 464 Hypoxia-related treatment resistance, 465, 465f Hypoxic ischemic encephalopathy, pediatric PET and PET/CT for, 447 I Ictal PET, 493, 493f Ileum carcinoid, cardiac metastasis of, [68Ga]DOTA-NOC/DOTA-TOC receptor PET/CT of, 426, 427f Image artifacts See Artifacts Image fusion, 111–115 MR-PET-SPECT, 113, 113f PET/CT, 111–113 in carbon-11-choline PET and CT, 112–113, 113f prospective “hardware” registration and motion artifact in, 111–112 retrospective registration in, 112 SPECT-MR, 113–115, 114f Image processing, 69–102 compartmental modeling in, 83–98 (See also Compartmental modeling) coregistration of 3-D data sets in, 98–102 intersubject, 102 intrasubject, intermodality, 100–102, 101f, 102f intrasubject, intramodality, 100 overview, 98–100 image reconstruction from projections in, 69–83 (See also Image reconstruction from projections) Image quality, PET, 54, 55f Image quantification, PET, 54–55, 56f Image reconstruction artifacts of, 165–167, 166f–167f compartmental modeling in, 83–98 (See also Compartmental modeling) Image reconstruction from projections, 69–83 for CT, 60 data corrections in, 77–83 attenuation, 80–82, 80f, 81f detector dead time, 78 gating, 82–83 normalization, 77–78 random and multiple coincidences, 78–79, 79f scattered coincidence events, 79–80 for 3-D PET, 74–77 3-D filtered back-projection with reprojection in, 75 3-D projection data in, 75 Fourier rebinning in, 76 fully 3-D iterative approaches in, 76 rebinning algorithms in, 75–76 time of flight in, 76–77 historical background on, 70 overview of, 69–70 reconstruction algorithms in, 70–74 filtered back-projection in, 71–73, 72f, 73f iterative reconstruction in, 73–74 projection data in, 70–71, 70f, 71f reduction in computational load in, 74 Imaging targets, 634–635 Imatinib, for gastrointestinal stromal tumors, 402–403 Immune-compromised, FDG PET/CT of infection and inflammation in, 626–627 Incident particles, Infantile spasms, 492–493 Infarction hemorrhagic, pediatric PET and PET/CT for, 447 myocardial, 565 imaging reinnervation after, 612 myocardial neurotransmitter imaging of, 612 Infection, pediatric PET and PET/CT for, 457 Infection and inflammation, FDG PET/CT of, 619–630 for cardiorespiratory infectious processes, 629 FDG uptake mechanism in, 619–620 for fever of unknown origin, 622–624, 624f for focal soft tissue infections, 624–625 for foreign body inflammatory reaction, 629 in immune-compromised, 626–627 for infection superimposed on malignancy, 626–627 inflammation in children, 457 [18F]-FDG uptake in, 154, 159f–166f, 163, 165 for inflammatory bowel disease, 627–629, 628f leukocytes in, FDG-labeled, 629–630 musculoskeletal, 620–622, 621f for inflammatory joint disease, 622, 623f for joint prosthesis infection, 621–622 for metallic implant infection, 621–622 for osteomyelitis diagnosis, 620–621, 621f, 623f for sarcoidosis, 627 technical aspects of, 619–620 vascular, 625–626 for vascular graft infection, 625, 626f for vasculitis, 625 for vulnerable atherosclerotic plaque, 625–626 Infection and inflammation, PET/CT of, 68Ga and 68 Ga-labeled peptides in, 630 Inflammatory bowel disease FDG PET/CT of, 627–629, 628f [18F]-FDG uptake in, 148, 148f Inflammatory joint disease FDG PET/CT of, 622, 623f [18F]-FDG uptake in, 143 Injection, of [18F]-FDG for cancer imaging, 124–125 Instrumentation, PET, 48–52 attenuation in, 52, 52f, 53f basic PET scanner in, 48–50 design of, 49–50, 50f overview of, 48–49, 49f degrading factors in, 50–52, 51f Instrumentation, PET/CT, 52–57 fundamentals of, 52–54, 53f–55f image quality in, 54, 55f image quantification in, 54–55, 56f in time of flight PET, 55–57, 56f Integrin activation inhibitors, 678 Integrin expression, imaging of, 680–686, 681f, 683f–685f Integrins, 678, 680 Intensity-modulated radiation therapy (IMRT), 467 Intensity-modulated radiation therapy (IMRT), hypoxia-directed, 467–468, 468f LWBL053-3787G-IND[713-730].qxd 8/16/08 1:23 AM Page 721 Aptara Inc Index Interferon-␣, 678 Interictal H2[15O] cerebral blood flow PET studies, 493 Intersubject registration, 102 Intrasubject, intermodality registration, 100–102, 101f, 102f Intrasubject, intramodality registration, 100 Intraventricular hemorrhage, pediatric PET and PET/CT for, 447 Intussusception, 678 Inverse Fourier transform, 72 In vivo reporter systems, 650–652, 651f Iodide retention time, in tumors, 653–654 Iodide trapping, in thyroid, 652 Iodide uptake in malignant tumors, enhancement of, 652–655, 653f Iodine-124 (124I), Iodine, lithium on thyroid release of, 653–654 Iodine contrast agents, 132–133, 133f Iodine-125-iodobenzovesamicol, for presynaptic function imaging, 610 Irradiation, target, in PET radionuclides, 3–4 Ischemia, angiotensin II receptor imaging of, 671–672 Ischemic cardiomyopathy, PET myocardial viability evaluation in, 575–581 vs [11C]-acetate washout kinetics, 581 vs cardiac MRI, 580–581 vs H2[15O] and perfusable tissue index, 581 vs [13N]-ammonia, flow and retention, 581 vs other imaging methods, 580–581 overview of, 575 randomized controlled trials on, 580 vs [82Rb] washout kinetics, 581 Islet cell tumor See Neuroendocrine tumors Isotope, 47 Iterative approaches, fully 3-D, for 3-D PET, 76 Iterative reconstruction, 73–74 IV contrast, artifacts from, 234, 235f J Jejunum, GI stromal tumor of, 132f JHU75528, [11C], 36f, 37 Joint disease, [18F]-FDG uptake in, 143 Joint prosthesis infection, FDG PET/CT of, 621–622 K Kidney receptors, imaging, 669–671, 670f, 671f Kidneys See also Renal entries Kidneys, PET of, 661–672 clinical protocols for, 661 functional and molecular imaging applications of, 661 molecular imaging in, 667–672 of enzymes, 669 of ischemia and remodeling, 670f, 671–672 of metabolism, 663f, 668–669 of receptors, 669–671, 670f, 671f of transporters, 667–668, 667f prospects of, 672 radiopharmaceutical kinetic properties for, 661 radiopharmaceuticals for, 662 rationale for use of, 661–662 for renal blood flow and cortical function imaging, 661 tracer kinetic models in, 662–667 (See also Renal radiopharmaceuticals) of chemical microspheres, 663f–665f, 664–666 (See also Chemical microspheres) of freely diffusible tracers, 662–664, 663f, 664b of glomerular filtration, 666 of radioligands, 666–667 types of, 662 use of, 662 Kinetic modeling approach, challenges with, 106 Ktrans, 680 L Label position, comparison of, in same molecule, 22–23, 23f Lactate oxidation, 590, 590f Language function, PET and PET/CT mapping of, 493 Larson-Ginsberg index, 108 Laryngeal muscles, [18F]-FDG distribution in, 141, 143f Late gadolinium enhancement (LGE), for myocardial viability imaging, 580–581 Least-squares estimation, 95–96, 96f Lennox-Gastaut syndrome, 493 L-Leucine, [11C-carboxyl], 34, 34f Leukoencephalopathy, FDG PET/CT of infection in, 627 Levosimendan, for congestive heart failure, 600–601, 600f Lewy body dementia, 484, 485t dopaminergic neurochemical imaging for differential diagnosis of, 487–488, 487f metabolic patterns of, 510–512, 512f Life span, 500 Lifestyle modification, PET myocardial perfusion evaluation of, 557 Lines of response (LORs), 48, 70 Lipid-lowering therapy, PET myocardial perfusion evaluation of, 556–557 List mode acquisition, 661 Liver metastasis, of pancreatic neuroendocrine tumor, [68Ga]-DOTA-NOC/DOTA-TOC receptor PET/CT of, 429, 432f Lung cancer, 248–257 epidemiology of, 248 management of, 248 smoking and, 248 Lung cancer, PET and PET/CT of for radiation therapy planning, 191–193 for treatment response monitoring, 180–181, 180t, 181f, 182f Lung cancer imaging, PET and PET/CT of anatomolecular [18F]-FDG in, 126–127, 127f for mesothelioma, 256–257, 257f for non–small cell lung cancer, 251–254 metastasis stage of, 252–254, 253f node stage of, 251–252, 252f restaging of, 254, 254f tumor stage of, 251 other tracers in, 257 for pleural disease, 255–257, 256f, 257f for pulmonary nodule evaluation, 248–251, 249f, 250f for radiation therapy planning, 191–193 for small cell lung cancer, 255, 255f for solitary pulmonary nodules, 248–251 CT in, 248–249 evaluation of, 248–251, 249f, 250f FDG PET/CT in, 249–251, 249f, 250f FDG PET in, 249, 249f, 250f multidetector CT with dynamic contrast enhancement in, 249–250 tissue sampling in, 249 for talc pleurodesis, 256, 256f for treatment response monitoring, 180–181, 180t, 181f, 182f Lymph nodes artifacts from calcification of, 234, 236f 721 inflammatory response of, [18F]-FDG uptake in, 165, 165f–166f staging of, for radiation oncology, 190 Lymphoid tissue [18F]-FDG distribution in, 140f, 151–153, 156f–157f head and neck, physiologic FDG activity in, 223, 224f Lymphoma, malignant diagnostic criteria in, 263 staging of, 260–261, 261f Lymphoma, malignant, PET and PET/CT of, 260–267 for early response assessment, 265–266, 266t FDG PET as surrogate marker for drug treatment benefit in, 707, 707f novel functional imaging approaches in, 266–267 for post-chemotherapy and/or radiotherapy evaluation, 263–265, 264f, 265t for proliferative activity, 267, 268f, 269f for radiation therapy planning, 194f, 195 response monitoring relevance in, 261–262 technical considerations in, 262, 262t for treatment remission assessment, 262–263, 263f, 264f for treatment response monitoring, 173–176, 174t, 175f Lymphoma in children, PET and PET/CT of, 451–452, 451f, 452f M Magnetic resonance angiography (MRA), of renal artery stenosis, 661 Magnetic resonance imaging (MRI) cardiac, vs PET myocardial viability evaluation of ischemic cardiomyopathy, 580–581 for myocardial energy metabolism assessment, 592 of myocardial viability, 580–581 Major depressive disorder, SPECT and PET of, 520–523, 522f antidepressant drug occupancy studies in, 523, 524f dopamine transmission in, 523 serotonin transmission in, 520–523, 522f Malignancy See also specific types infection superimposed on, FDG PET/CT of, 626–627 Malignant melanoma classification of, 275 clinical course of, 276 diagnosis and microstaging of, 275 distribution of, 276 epidemiology of, 275 hematogenous spread of, 276 prognostic factors in, 275 staging of, 276 Malignant melanoma, PET and PET/CT of, 275–285 whole-body, 276–279, 277f–278f, 280f–284f whole-body, effectiveness of, 280–281, 284 Marimastate, 679 Mass number, 47 Mastication muscles, physiologic FDG activity in, 223, 225f Matrix metalloproteinase (MMP) inhibitors, 679 Matrix metalloproteinases (MMPs), 679, 686 Medullary thyroid cancer, 245 Melanoma, malignant See Malignant melanoma Membrane transport, 667 Meningioma, [68Ga]-DOTA-NOC/DOTA-TOC receptor PET/CT of, 426f Menstrual ovulation, endometrium, [18F]-FDG uptake in, 149, 159f LWBL053-3787G-IND[713-730].qxd 8/16/08 1:23 AM Page 722 Aptara Inc 722 Index Mesothelioma, malignant pleural, 256–257, 257f Metabolic changes, after therapeutic intervention, 647 Metabolic imaging, 480 Metabolic modulators, for congestive heart failure, 601 Metabotropic glutamate receptors (mGluR), 37 Metabotropic glutamate receptors (mGluR) radiotracers, 36f, 37 Meta-hydroxyephedrine, 11C ([11C-HED]), for presynaptic function imaging, 609–610, 609f Metaiodobenzylguanidine (MIBG) drug withdrawal with, 413, 413t for neuroendocrine tumors, 413, 415t Metaiodobenzylguanidine (MIBG), [123I] for presynaptic function imaging, 609, 609f in SPECT, 607 Metaiodobenzylguanidine (MIBG), [131I] mechanism of uptake of, 654 use of, 654 Metallic devices, artifacts from, 234, 235f Metallic implant infection, FDG PET/CT of, 621–622 Metaraminol, [18F] (FMR), for presynaptic function imaging, 609, 609f, 610t Metastasis, variable survival with, 475 Methamphetamine abuse, PET of, 527–528 Methane, [11C], 19 Methionine [11C], 34, 34f, 473 monitoring tumor response with, 170–171 Methylation, gene, alterations in, 117 Methylenedioxymethamphetamine (MDMA, ecstasy) abuse, SPECT and PET of, 528 d-threo-Methylphenidate, [11C], 18, 26, 27f Methylquinuclidinyl benzilate (MQNB), [11C], for postsynaptic receptor imaging, 610 Microspheres, chemical, 663f–665f, 664–666 Mild cognitive impairment (MCI), 690–691 metabolic patterns of, 508–509, 509f, 513f PET amyloid imaging of, 694f, 695–696, 696f Mitogen-activated protein kinase (MAPK), 464 Molecular imaging, 667 Molybdenum-99/technetium-99m (99Mo/99mTc) generator, Monitoring treatment response, 169–184 issues in, 169 PET clinical research and experience in brain tumors, 172–173, 172t, 173f breast cancer, 178–179, 178t, 179f, 180f gastrointestinal cancer, 181–183, 182f, 183t genitourinary cancer, 183–184 head and neck cancer, 176–178, 176t, 177f lung cancer, 180–181, 180t, 181f, 182f lymphoma, 173–176, 174t, 175f PET imaging timing in, 169–170, 170t PET tumor measurement quantitation in, 171–172 tracers for blood flow, 171 FDG and tumor glycolysis, 170 labeled drugs, 171 methionine and protein synthesis, 170–171 thymidine and nucleoside analogues, 171 Monoamine oxidase (MAO) in brain dopamine system, 27–28, 28f on dopamine, 25 in smokers, 529 Monoamine oxidase (MAO) B enzyme inhibition, as PET target for drug development, 640–641, 640t, 641f, 642f Monoamine oxidase (MAO) inhibitor drugs, 27 Monoclonal antibody labeling, label incorporation in, Monoclonal gammopathy of unknown significance, 267 Motion artifact, 66–67, 66f, 111–112 Movement disorders, PET and PET/CT of, 483–488 choreiform, 486 cortical metabolic/blood flow changes in, 483, 484t corticobasal degeneration, 485–486, 486f dopaminergic neurochemical imaging in, 486–487, 487f for atypical parkinsonian disorders, pre- and postsynaptic, 487, 487t for parkinsonian or Lewy body dementia differential diagnosis, 487–488, 487f essential tremor, 486 glucose metabolism in, 483, 483t Huntington disease, 486 multiple system atrophy, 486 Parkinson disease, 483–484 parkinsonian or Lewy body dementia, 484, 485t progressive supranuclear palsy, 485, 485f MPA, [11C], 33, 33f MRB, (S,S)[11C]-, 36, 36f MR-PET-SPECT, image fusion in, 113, 113f Mucosal tissue, physiologic FDG activity in, 223, 223f Multidrug resistance proteins (MRP2-MRP5), 667 Multinodular goiter, [18F]-FDG uptake in, 149, 153f Multiple coincidences, 78–79, 79f Multiple myeloma clinical manifestations of, 267 diagnosis in, 268–269 epidemiology of, 267 Multiple myeloma, PET and PET/CT of, 267–271 for extramedullary disease, 268, 272f for hypercalcemia and bone disease, 268 for staging and risk assessment, 269–272, 270f–272f Multiple-row detector CT (MDCT), 60 design arrays for, 60–63, 61f–62f pitch in, 63, 64f Multiple system atrophy (MSA), 486 Multiple system atrophy (MSA) imaging, 487, 487t Mu opiate receptors, in cocaine abuse, 527 Muscarinic cholinergic receptors (mACHR), 31, 608 Muscarinic cholinergic receptors (mACHR) radiotracers, 31, 32f Muscles, head and neck, physiologic FDG distribution in, 223, 224f–225f Musculoskeletal infection and inflammation, FDG PET/CT of, 620–622, 621f for inflammatory joint disease, 622, 623f for joint prosthesis infection, 621–622 for metallic implant infection, 621–622 for osteomyelitis diagnosis, 620–621, 621f, 623f Myocardial blood flow, 541 absolute assessment of, 548 hyperemic, PET myocardial perfusion evaluation of, 549, 550f, 550t Myocardial blood flow tracers, 542–544, 542t, 543f carbon-11-butanol, 542t, 544 copper-62 PTSM, 542–544, 542t fluorine-18 fluorobenzyl triphenyl phosphonium, 542t, 543f, 544 nitrogen-13-ammonia, 542, 542t, 543f oxygen-15-water, 542t, 544 rubidium-82, 542, 542t, 543f Myocardial efficiency, 598 with congestive heart failure, 599–601, 600f with hypertension, 598–599 Myocardial energy metabolism assessment, 591–592 Myocardial infarction, 565 imaging reinnervation after, 612 neurotransmitter imaging of, 612 Myocardial ischemia, neurotransmitter imaging of, 612 Myocardial metabolism, 589–591, 590f ATP in, 589–590, 590f carbohydrate oxidation in, 590 efficiency of, 591 fatty acid oxidation in, 590, 590f glucose and lactate oxidation in, 590 tricarboxylic acid (TCA) cycle in, 590–591, 590f Myocardial neurotransmitter imaging, 607–615 clinical applications of, 612–615 congestive heart failure, 615 diabetes mellitus, 613–614, 613f myocardial ischemia and infarction, 612 reinnervation after heart transplantation, 614–615, 614f reinnervation after myocardial infarction, 612 ventricular arrhythmia, 612–613 data interpretation in, 611–612, 611f, 612f imaging protocols for, 610–611 radiopharmaceuticals for, 609–610, 609f, 610t in postsynaptic receptor imaging, 610 in presynaptic function, 609–610, 609f, 610t Myocardial oxidative metabolism, in hypertrophic cardiomyopathy, 602 Myocardial oxygen consumption assessment, PET, 592–597 carbon-11-acetate, 592–595, 593f, 594f (See also Carbon-11-acetate) 15 O2 PET, 595–597, 595f (See also Oxygen-15 [15O2] PET) special features of PET in, 597 Myocardial perfusion evaluation, PET, 541–559 accuracy of, 542–543 for cardiac resynchronization therapy, 559 for cardiac stem cell therapy, 559 clinical applications of, 552–558 antioxidant therapy for smokers, 557 cigarette smoking, 557 coronary artery disease, diagnosis, 552, 553t, 554f, 554t coronary artery disease, myocardial blood flow reserve assessment, 556 coronary artery disease, prognosis, 552, 554f, 555t coronary flow reserve vs risk factors, 556 cost-effectiveness, 552, 556 diabetes mellitus, 557 endothelial dysfunction with coronary risk factors, 558 hyperlipidemia and lipid-lowering therapy, 556–557 hypertension and antihypertensive therapy, 557–558 lifestyle modification and exercise training, 557 therapy evaluation, 556 clinical indications for, 544, 544f integrated PET/CT, 550–552, 551f myocardial blood flow tracers in, 542–544, 542t, 543f (See also Myocardial blood flow tracers) for new therapy assessment, 559 for nonatherosclerotic heart disease, 558–559 dilated cardiomyopathy, 558 heart transplant, 558 hypertrophic cardiomyopathy, 558 pediatrics, 546f, 558–559 LWBL053-3787G-IND[713-730].qxd 8/16/08 1:23 AM Page 723 Aptara Inc Index syndrome X, 558 valvular heart disease, 558 protocols for absolute myocardial blood flow assessment, 548 common artifacts, [13N]-tritium, 543f, 546–547 common artifacts, [82-Rb], 547–548 coronary flow reserve, 549, 550f, 550t endothelial function, 549–550, 551t exercise stress, 545–546 hyperemic myocardial blood flow, 549, 550f, 550t image acquisition and processing, [13N]ammonia, 546 image acquisition and processing, [82-Rb], 546, 546f [13N]-tritium blood flow quantification, 548 [15O]-water myocardial blood flow quantification, 548–549, 549f patient preparation for imaging, 544–545 pharmacological stress, dobutamine, 545 pharmacological stress, vasodilator pharmacological, 545, 545f semiquantitative image interpretation, 546, 547f, 548f use of, 541 Myocardial stunning, 565–566 Myocardial viability, for ischemic cardiomyopathy FDG PET imaging on clinical decision marking and its cost-effectiveness, 575–580, 580f in prediction of improved clinical outcomes after revascularization, 577–578, 578f, 579f, 579t of improved heart failure symptoms after revascularization, 576–577 of recovery of regional/global LV dysfunction after revascularization, 576, 576f, 577t Myocardial viability evaluation, PET, 565–582 future directions of, 582 gated FDG PET imaging of, 575, 575f glucose metabolism in, 565 hibernating myocardium and, 565–567, 566f, 567t, 568f image acquisition and analysis in, 567–569 approaches in, 567 cardiac FDG PET imaging protocols in, 568 patient preparation in, 567–568 image interpretation in, 569–575 image reporting, 574 importance of, 569 normal perfusion/normal FDG (normal pattern), 571f–573f, 573–574 normal perfusion/reduced FDG (reverse mismatch), 571f, 574 poor image quality, 574–575 protocol for, 569, 569f–572f quantifying myocardial FDG uptake and glucose utilization, 575 reduced perfusion/maintained or increased FDG (mismatch), 566f, 567t, 568f, 569, 569f, 573f reduced perfusion/partially reduced FDG (partial mismatch), 570f, 573 reduced perfusion/reduced FDG (match), 570f, 573 right ventricular uptake, 574 infarction and, 565 for ischemic cardiomyopathy, 575–581 vs [11C]-acetate washout kinetics, 581 vs cardiac MRI, 580–581 vs H2[15O] and perfusable tissue index, 581 vs [13N]-ammonia, flow and retention, 581 vs other imaging methods, 580–581 overview, 575 randomized controlled trials on, 580 vs [82Rb] washout kinetics, 581 myocardial stunning and, 565–566 other applications of, 582 stress FDG imaging of, 581–582 Myocardium, [18F]-FDG distribution in, 140, 141f Myositis ossificans, [18F]-FDG uptake in, 153–154, 158f N 13 N, NAD-299, [11C], synthesis of, 19 NaI gamma cameras, in PET imaging, 122 [N-11C-methyl]piperidinyl acetate ([11C]AMP), 31, 32f [N-11C-methyl]piperidinyl propionate ([11C]PMP), 31, 32f Neck, normal [18F]-FDG uptake in, 139, 140f NEFA, 18F, 32, 32f Neovasculature imaging, 676–687 angiogenesis cascade in, 677–678 (See also Angiogenesis) antiangiogenic therapeutic strategies and, 678–679 of functional markers of angiogenesis, 679–680 blood flow, 679–680 blood volume and vascular permeability, 680 of molecular markers of angiogenesis, 680–686 extra-domain B of fibronectin, 686 integrin expression, 680–686, 681f, 683f–685f matrix metalloproteinases, 686 promising new targets, 686 vascular endothelial growth factors and its receptors, 686 perspectives on, 687 techniques for [15O]-water in, 676–677 potentials of, 676 problems with, 676–677 results of, 677 Neovastat, 679 Nephrogenic systemic fibrosis, from gadolinium, 581 Neuroacanthocytosis, 486 Neuroblastoma, pediatric PET and PET/CT of, 452–454, 453f, 454f Neurochemical imaging studies, 479 Neuroendocrine carcinoma See Neuroendocrine tumors Neuroendocrine tumors classification of, 411, 412t clinical manifestations of, 412 histology of, 411–412 incidence and pathophysiology of, 411 origin of, 411, 412t radionuclide imaging methods for, 421 Neuroendocrine tumors, PET and PET/CT of, 411–434 [11C]-epinephrine in, 434 [11C]-hydroxyepiphedrine in, 434 [11C]-5-hydroxytryptamine (HTP) PET in, 433 clinical indications for, 421 clinical studies of, 421–434 [68Ga]-DOTA-NOC/DOTA-TOC receptor PET/CT in, 422–431, 423f–431f (See also DOTA-NOC/DOTA-TOC receptor PET/CT, [68Ga]) nuclear medicine physician in tumor management and, 421–422, 422t 723 [64Cu]-TETA-octreotide in, 433 for diagnosis, 412–421 [68Ga] labeling of DOTA in, 420–421 history and examination in, 412 imaging in, 412 PET radiopharmaceuticals for, 413–420, 414t–415t (See also Radiopharmaceuticals, for neuroendocrine tumors) radionuclide imaging in, 413 [18F]- and [11C]-dihydroxyphenylalanine and [18F]-fluorodopamine PET in, 431–433, 433f [18F]-fluorodeoxyglucose PET in, 433–434 future perspectives on, 434 Gluc-Lys ([18F])-FP-TOCA PET in, 433 vs other radionuclide imaging methods, 421 Neurokinin-1 receptors, radiotracers for, 36f, 37 Neurology See also specific disorders pediatric PET and PET/CT in, 445–447 Neuronal imaging, after stroke, 490–491 Neuropeptide Y, 608 Neuroreceptors See also specific receptors as targets for PET drug development, 637, 638f Neurotransmitter imaging, myocardial, 607–615 See also Myocardial neurotransmitter imaging Neurotransmitter systems, in psychiatric disorders, 516–517 See also Psychiatric disorders Neutrino, 47 Neutron number, 47 NFEP, [18F], 33, 33f Nickel-64 [64Ni], Nicotine, [11C], 33, 33f Nicotine abuse, molecular imaging of, 528–529 Nicotinic acetylcholine receptors (nAChR), 32–33 radiotracers for, 32–33, 33f Nigrostriatal dopamine nerve terminal, 486, 487f Nitrogen-13 [13N], 4t, in PET radiotracers, 17t, 37 physical properties of, 17, 17t production reactions for, properties of, 4t, radioisotope separation for, targetry for, Nitroimidazole compounds, for hypoxia imaging, 466 NMDA (N-methyl-D-aspartate) receptors, radiotracers for, 36f, 37 NMI-EPB, [18F], 33, 33f No carrier added (NCA), 17–18 Noise equivalent count (NEC), Nomifensine, [11C], 26, 27f Non-Hodgkin’s lymphoma in children, PET of, 451–452, 451f Nonlinear regression techniques, in parameter estimation, 95–96, 96f Non–small cell lung cancer, 251–254 FDG PET as surrogate marker for drug treatment benefit in, 706–707, 706f metastasis stage of, 252–254, 253f node stage of, 251–252, 252f restaging of, 254, 254f tumor stage of, 251 Nonsuicide reporter genes, imaging gene expression with, 649–650, 649f Norepinephrine, 607–608, 608f Norepinephrine transporter (NET) in neuroblastoma, pheochromocytoma, and neuroendocrine tumors, 118 radiotracers for, 36, 36f LWBL053-3787G-IND[713-730].qxd 8/16/08 1:23 AM Page 724 Aptara Inc 724 Index Normalization, 77–78 Nuclear magnetic resonance (NMR) spectroscopy, for myocardial energy metabolism assessment, 591 Nuclear reaction, Nuclear reaction cross section, 1–2, 2f, 3f Nucleophilic aromatic substitution reaction, for 18 F-substituted compounds, 21 Nucleus, compound model of, Nuclide, 47 O Obsessive compulsive disorder (OCD), 525 Occupational lung disease, [18F]-FDG uptake in, 164–165, 165f Oligonucleotides antisense, imaging of, 655–656 cell entry of, 655 Omental metastases, pediatric PET and PET/CT for, 450f Oncology hypoxia imaging in, 465, 465f pediatric PET and PET/CT in, 448–457 Opiate system, brain, radiotracers for, 29–30, 30f Organ density, in Hounsfield (H) units, 131, 132f Organic anion transporters, 667 Organic anion transport (OAT) system, 668 Organic cation transporters, 667 Organ transplantation FDG PET/CT of infection after, 626–627 heart PET myocardial perfusion evaluation of, 558 reinnervation after, myocardial neurotransmitter imaging of, 614–615, 614f Osteoarthritis, FDG PET/CT of, 622, 623f Osteomyelitis diagnosis, FDG PET/CT of, 620–621, 621f, 623f Osteosarcomas, 398, 398t in children, PET of, 454–455, 456f Ovarian cancer, 355–364 CA125 screening for, 355 classification of, 355 CT, MRI, and ultrasound of, 356 diagnosis of primary carcinoma in, 357–358, 358t epidemiology of, 355 false-positives and false-negatives in, 357–358, 358t FDG PET as surrogate marker for drug treatment benefit in, 708 screening for, 357 staging of, 356 surveillance for, 360, 363t transvaginal ultrasound of, 355 Ovarian cancer, PET and PET/CT of FDG PET role in, 356–357 on management, 364 for monitoring therapy response, 359, 359f other PET radiotracers in, 363 for primary disease detection, 355–356 for prognosis evaluation, 360, 363 for restaging, 359–360, 360t, 361f–363f for staging, 358–359 for surveillance, 360, 363t Ovary, [18F]-FDG distribution in, 149, 152f [15O]-water See Oxygen-15 water [15O] Oxidation carbohydrate, 590 fatty acid, 590, 590f glucose, 590, 590f lactate, 590, 590f Oxygen extraction fraction, 488, 488t, 589 Oxygen homeostasis, cellular regulation of, 464 Oxygen metabolism, cerebral, in stroke, 488, 488t Oxygen-15 [15O], Oxygen-15 [15O2] PET, 595–597, 595f for congestive heart failure with hypertension, 599–601, 600f data analysis in, 596 data processing and modeling in, 595–596, 595f for myocardial efficiency assessment, 598 scanning protocol in, 595 sources of error and limitations of, 596–597 validation and experimental studies in, 596, 596f Oxygen-15 water [15O], 4t, 7–8 for imaging myocardial viability, 581 myocardial blood flow quantification with, 548–549, 549f as myocardial blood flow tracer, 542t, 544 neovasculature imaging with, 676–677 (See also Neovasculature imaging) of blood flow, 679–680 of blood volume and vascular permeability, 680 vs PET myocardial viability evaluation of ischemic cardiomyopathy, 581 in PET radiotracers, 17t, 37 physical properties of, 17, 17t production reactions for, properties of, 4t, radioisotope separation for, targetry for, P Pacemaker artifact, 67, 67f Palatine tonsils [18F]-FDG distribution in, 153, 157f normal [18F]-FDG uptake in, 139, 140f Pancreatic carcinoma CT of, 331 endoscopic ultrasonography of, 332 epidemiology of, 331 fine-needle aspiration biopsy of, 332 MRI of, 331 Pancreatic carcinoma, PET and PET/CT of, 331–338 for cystic endocrine neoplasms, 338, 338f for cystic pancreatic neoplasms, 336–338, 337f for detecting recurrences, 334–336, 336f limitations of, 333 for monitoring therapy, 336, 337f on patient management, 334 for preoperative diagnosis, 332–333, 332f for staging, 333–334, 334t, 335f Pancreatic neuroendocrine tumor, [68Ga]-DOTANOC/DOTA-TOC receptor PET/CT of, 429, 431f, 432f Pancreatitis, [18F]-FDG uptake in, 154, 162f Panic disorder, 524–525 Parameter estimation, in compartmental modeling, 95–97 nonlinear regression techniques in, 95–96, 96f specialized graphical approaches in, 96–97 use of, 95 without arterial input functions, 97 Paraneoplastic cerebellar degeneration (PCD), 439–441 Paraneoplastic neurological syndromes (PNS), 439–441 Parasympathetic nerve terminal, 608, 608f Parent exposure, to child’s radiation and radiopharmaceuticals, 444, 445t Parkinson disease, 483–484 dopaminergic neurochemical imaging of, 486–487, 487f metabolic patterns of, with dementia, 510–511 Parkinsonian dementia dopaminergic neurochemical imaging of, 487–488, 487f fundamentals of, 484, 485t Parotid glands normal [18F]-FDG uptake in, 139, 140f physiologic FDG activity in, 222, 222f Parotid gland tumors, [18F]-FDG uptake in, 154, 159f Particles bombarding, incident, Patlak analysis, 96–97 Pax8, 652 Pediatrics, PET and PET/CT in, 443–458 for cardiology, 447–448 history of, 443 for infection and inflammation, 457 myocardial perfusion evaluation of heart disease in, 546f, 558–559 for neurology, 445–447 epilepsy, 445–447, 446f hemorrhagic infarction, 447 hypoxic ischemic encephalopathy, 447 intraventricular hemorrhage, 447 normal brain development, 445, 446f other brain disorders, 447 for oncology, 448–457 bone tumors, 454–455, 456f brown adipose tissue FDG uptake in, 448–449 central nervous system tumors, 450–451, 451f embryonal rhabdomyosarcoma and omental metastases, 450f false-positives in, 448–449 FDG distribution in, 448, 449f growth plate uptake in, 448, 449f hematopoietic stimulating factors on FDG uptake in, 449, 450f lymphoma, 451–452, 452f neuroblastoma, 452–454, 453f, 454f PET vs PET/CT for, 448 rhabdomyosarcoma, 457, 457f skeletal muscle FDG uptake in, 449 soft tissue tumors, 457, 457f standardized uptake value in, 449–450 thymic rebound after chemotherapy in, 448, 449f thymus uptake of FDG in, 448, 449f Wilms’ tumor, 454, 455f parent exposure and distance from patient in, 444, 445t patient preparation in, 443 radiation dosimetry in, 444–445, 444t, 445t radiopharmaceuticals in, 444–445, 444t PE2I, [11C], 26–27 Pelvic geometry accommodation, 112, 113f Penumbra tissue, 489 Percutaneous catheterization, for myocardial energy metabolism assessment, 592 Percutaneous revascularization, for ischemic renal disease, 671 Percutaneous tube insertion, [18F]-FDG uptake in, 154, 159f Perfusable tissue index, 581 Perfusion, blood, 679 Personality disorders, SPECT and PET of, 525 PET (positron emission tomography), 479 for glucose and fatty acid metabolism assessment, 592 imaging device for, 122 LWBL053-3787G-IND[713-730].qxd 8/16/08 1:23 AM Page 725 Aptara Inc Index for myocardial energy metabolism assessment, 592 patient interview in, 123 patient preparation for, 122–123 patient selection for, 122 timing of, for monitoring treatment response, 169–170, 170t PET/CT See also specific topics advantages of, 58 alignment of, 58 challenges in development of, 58–59 CT optimization for, 131–137 (See also CT optimization for PET/CT) diagnostic advantages of, 131 fundamentals of CT in (See CT (computed tomography), in PET/CT) image fusion in, 111–113, 113f patient interview in, 123 patient preparation for, 122–123 patient selection for, 122 protocol for, 59, 63–64, 63f, 64t scan parameters in, 63–64, 63f, 64t schematic diagram of, 58, 59f utilization of, 58 PET/CT instrumentation See Instrumentation, PET/CT PET instrumentation See Instrumentation, PET P-glycoprotein, 667 Pharmacological studies See also specific drugs and disorders compartmental modeling for, 91–92, 91f Phenylephrine, [11C], for presynaptic function imaging, 610 Pheochromocytoma/paraganglioma, [68Ga]-DOTANOC/DOTA-TOC receptor PET/CT of, 426, 428f Phobia, social, 525 Phosphatidylinositol 3-kinase (PIeK), 464 Photomultiplier tubes (PMTs), 49, 50f Physics, positron, 47–48, 48f, 48t Physostigmine, [11C] ([11C]PHY), 31, 32f PIB, [18F], 35, 35f Pick disease, metabolic patterns of, 509t, 510, 510f Pilocytic astrocytoma, 212, 212f Pitch, 63, 64f Pittsburgh compound-B, 692–693, 692f Pittsburgh compound-B-negative control subjects, PET amyloid imaging of, 693–694, 694f Pittsburgh compound-B-positive control subjects, PET amyloid imaging of, 694f, 696–697 PK11195, [11C], 30–31, 31f Planar imaging, of neuroendocrine tumors, 421 Plasma, measuring radiotracer concentration in, 92–94, 93f Plasma cell neoplasms, 267 See also Multiple myeloma Pleomorphic xanthoastrocytoma, 213, 214f Pleural disease, 255–257, 256f, 257f Pleurodesis [18F]-FDG uptake in, 154, 161f talc, 256, 256f Pneumocystic jiroveci infection, FDG PET/CT of, 627 Polysome imaging, 656 Positron, 47 Positron annihilation, 47–48, 48f Positron decay, 47, 48t Positron emission tomography (PET) See PET (positron emission tomography) Positron emitters, short lived, physical properties of, 17, 17t Positron physics, 47–48, 48f, 48t Posterior cingulate cortex, 481 Posttraumatic stress disorder (PTSD), 525 Posttreatment remission assessment, 261 Pressure–volume relationship, in heart metabolism, 591 Primary sclerosing cholangitis, 341 Probe, 634 See also specific probes characteristics of, for PET drug development, 637, 637t development of, 634 Progressive supranuclear palsy (PSP), 485, 485f metabolic patterns of, 509–510, 509t, 511f pre- and postsynaptic dopaminergic neurochemical imaging of, 487, 487t Projection, PET, 48–49, 49f, 70 See also Image reconstruction from projections Projection data for 3-D PET, 75 in reconstruction algorithms, 70–71, 70f, 71f Projection rays, PET See Projection, PET Projection sinogram, 71, 71f Prompt coincidence window, 79 Prompt events, 51 Prostate cancer See also Genitourinary malignancies bone scan for, 374 CT imaging of, 373 epidemiology of, 372 FDG PET as surrogate marker for drug treatment benefit in, 708 metastasis of, 373 MRI imaging of, 373–374 phosphocholine plus glycerophosphocholine (PC+GPC) in, 373–374 Prostate cancer, PET and PET/CT of, 372–379 clinical states model and, 368f, 374–379 androgen receptor in, 378–379, 378f for detection and screening, 374–375, 374f for guiding chemotherapy with metastases, 377, 378f indications for, 379 prognostic value of, 377–378 for PSA relapse after treatment with curative intent, 375 for staging, primary, 375–377, 376f–377f for recurrence, 372–373 for treatment, 372–373 Prosthesis infection, FDG PET/CT of, 621–622 Protein interaction analysis, 650–652, 651f Protein–protein interaction imaging, 650–652, 651f Protein synthesis, 34 Protein synthesis radiotracers, 34–35, 34f Proteome, altered, in cancer, 117 Protocol, in PET/CT, 59, 63–64, 63f, 64t Proton number, 47 Pseudosubstrate, 662 Psychiatric disorders history of, 516 neurotransmitter systems in, 516–517 Psychiatric disorders, SPECT and PET of, 516–530 See also specific disorders affective disorders, 520–524 bipolar disorder, 523–524 major depressive disorder, 520–523, 522f anxiety disorders, 524–525 conduct disorder, 526 personality disorders, 525 schizophrenia, 517–520, 518f substance abuse, 526–530 Pterygoid muscles, physiologic FDG activity in, 223, 225f PTSM, 62Cu as myocardial blood flow tracer, 542–544, 542t renal PT imaging with, 666 725 Pulmonary nodule See also Solitary pulmonary nodules chest CT for detection of, 136 evaluation of, 248–251, 249f, 250f Pyogenic infection, [18F]-FDG uptake in, 154, 161f Pyruvate dehydrogenase kinase (PDK), 119 Q Quality, PET image, 54, 55f Quality control, in PET/CT, 65 Quantification, PET image, 54–55, 56f Quantitation, in PET tumor measurements, 171–172 Question-based drug development, 634, 635t Q value, 2, 2f R Raclopride, 11C, 25, 26f Radiation dose in CT, 65–66, 65t in pediatrics, 444–445, 444t, 445t in PET/CT, 65–66, 65t Radiation dosimetry, in children, 444–445, 444t, 445t Radiation exposure, in PET/CT, 137 Radiation oncology definitive treatment with, 187 risks of, 187 treatment planning in, 187–188 Radiation oncology, PET and PET/CT in, 187–195 curative radiation therapy in, 187–188 in patient selection for curative radiation, 188–190 distant metastasis detection in, 189–190 general principles of, 188–189, 188f lymph node staging in, 190 in radiation therapy planning, 190–195 for esophageal cancer, 194 for head and neck cancer, 192f, 193–194, 193f for lung cancer, 191–193 for lymphoma, 194f, 195 movement in, 190 for other cancers, 195 process in, 190–191 Radiation pneumonitis, [18F]-FDG uptake in, 163, 164f Radiation therapy sequela, [18F]-FDG uptake in, 163, 163f, 164f Radioactive decay, 47, 48t Radioactivity, blood-borne, 95 Radiohalogenated peptides, 680–681, 681f Radioligand, 661, 666 Radionuclide decay, production on, Radionuclide generator equations, PET, 10–11 Radionuclide generator systems, 9–10 Radionuclide production, PET, 1–11 See also specific radionuclides bromine-75 (75Br), carbon-11 (11C), 4t, 6–7, 6f copper-61 (61Cu), copper-64 (64Cu), 8–9 decay characteristics of, 4, 4t fluorine-18 (18F), 4t, 5–6, 6f (See also Fluorine18 [18F]) gallium-68 (68Ga), generator equations for, 10–11 generator-produced positron-emitting, 9–10, 9t iodine-124 (124I), nickel-64 (64Ni), nitrogen-13 (13N), 4t, novel solid targets for, 8–9 overview of, oxygen-15 (15O), 4t, 7–8 LWBL053-3787G-IND[713-730].qxd 8/16/08 1:23 AM Page 726 Aptara Inc 726 Index Radionuclide (Continued) process of, 1–3 eliminating radionuclidic impurities in, 2–3, 3f enriched targets in, nuclear reaction cross section in, 1–2, 2f, 3f rubidium-82 (82Rb), 10 specific activity in, 4–5, 4t target irradiation in, 3–4 traditional radioisotopes, zinc-62 (62Zn), Radionuclides definition of, 47 half-life of, 47, 48t physics of, 47 Radionuclidic purity, 2–3, 3f Radiopharmaceuticals See also Radiotracers/ tracers; specific radiopharmaceuticals in children, 444–445, 444t in pediatrics, 444–445, 444t, 445t renal, 662 chemical microspheres, 663f–665f, 664–666 freely diffusible tracers, 662–664, 663f, 664b kinetic properties of, 661 Radiopharmaceuticals, for neuroendocrine tumors, 413–420, 414t–415t biogenic amine production and storage in, 419, 419f bombesin in, 419, 420t catecholamine transport pathway in, 413t, 419 cholecystokinin (CCK), 420, 420t gastrin-releasing peptide receptors in, 419 germanium-68/gallium-68 generator in, 420 glucose metabolism in, 419 MIBG, 413, 415t (See also Metaiodobenzylguanidine (MIBG), [131I]) drug withdrawal with, 413, 413t other tumor-produced peptides in, 419–420, 420t serotonin production pathway in, 418–419, 419f somatostatin receptor expression in, 413, 416–418, 416t, 417t, 418f (See also Somatostatin receptor) targets for, 413 VIP, 420, 420t Radiotracers/tracers See also specific tracers for acetylcholinesterase, 31–32, 32f for aggregated amyloid (Alzheimer’s disease), 35, 35f for ␣3 imaging, 680–682, 681f for Alzheimer’s disease, 35, 35f for amino acid transport, 34–35, 34f for amyloid imaging, PET, 691–693 carbon-11-Pittsburgh compound-B, 692–693, 692f carbon-11 stilbene, 692f, 693 fluorine-18 radiofluorinated derivative (FDDNP), 691–692, 692f monoclonal antibody fragments, radiolabeled, 691 for benzodiazepine system, 30–31, 31f for blood vessel formation, 475–476 for brain dopamine system, 25–28 (See also under Dopamine system, brain) for breast cancer, PET and PET/CT of, 474, 474f for cancer imaging, newer, 472–476 (See also Cancer imaging, newer tracers for) for cannabinoid receptors, 36–37, 36f for cellular proliferation, 475, 475f chemistry of, PET and PET/CT, 16–38 (See also Radiotracer/tracer chemistry, PET and PET/CT) for cholinergic system, 31–33, 32f, 33f (See also Cholinergic system, radiotracers for) definition of, 661 for dementia, 505 for DNA synthesis, 35, 35f for dopamine system, brain, 25–28 (See also Dopamine system, brain, radiotracers for) for glomerular filtration, 666 for glutamate system, brain, 36f, 37 high specific activity, 17 for 5-HT1A receptors, 29 for 5-HT2A receptors, 28–29, 28f for hypoxia imaging, 476, 476f labeled drugs as, 171 for metabotropic (mGluR) glutamate receptors, 36f, 37 for metabotropic glutamate receptors (mGluR), 36f, 37 for monitoring cancer treatment response, 170–171 for monitoring tumor response methionine and protein synthesis, 170–171 thymidine and nucleoside analogues, 171 for muscarinic cholinergic receptors (mACHR), 31, 32f for myocardial blood flow, 542–544, 542t, 543f for neurokinin-1 receptors, 36f, 37 for neurotransmitter systems, PET and PET/CT, 25–34 (See also Radiotracers/tracers, for neurotransmitter systems, PET and PET/CT) for nicotinic acetylcholine receptors (nAChR), 32–33, 33f for NMDA (N-methyl-D-aspartate) receptors, 36f, 37 for norepinephrine transporter (NET), 36, 36f for opiate system, brain, 29–30, 30f for protein synthesis, 34–35, 34f radiotracer chemistry in, rapid, 16–21 (See also Radiotracer/tracer chemistry, rapid) for serotonin system, brain, 28–29, 28f, 29f for serotonin transporter, 29, 29f for signal transduction pathways, 33–34, 34f for substance P, 36f, 37 time in synthesis of, 16 Radiotracers/tracers, for neurotransmitter systems, PET and PET/CT, 25–34 benzodiazepine system, 30–31, 31f brain dopamine system, 25–28 dopamine and vesicular transporters in, 26–27, 27f dopamine metabolism in, 23f, 25 dopamine receptors in, 25–26, 26f monoamine oxidase in, 27–28, 28f brain serotonin system, 28–29, 28f, 29f cholinergic system, 31–33, 32f, 33f acetylcholinesterase, 31–32, 32f muscarinic cholinergic receptors, 31, 32f nicotinic acetylcholine receptors, 32–33, 33f signal transduction pathways, 33–34, 34f Radiotracer/tracer chemistry, PET and PET/CT, 16–38 See also specific radiotracers for aggregated amyloid (Alzheimer’s disease), 35, 35f for amino acid transport and protein synthesis, 34–35, 34f for brain glutamate system, 36f, 37 for cannabinoid receptors, 36–37, 36f design and mechanisms in, 21–22, 22f deuterium isotope effects in, 24, 24f for DNA synthesis, 35, 35f 124 I in, 37 kinetics in, 22 for neurokinin-1 receptors, 36f, 37 for neurotransmitter systems, 25–34 (See also Radiotracers/tracers, for neurotransmitter systems) 13 N in, 17t, 37 for NMDA receptors, 36f, 37 for norepinephrine transporter, 36, 36f 15 O in, 17t, 37 rapid, 16–21 (See also Radiotracer/tracer chemistry, rapid) specificity and saturability in, 22 for substance P, 36f, 37 urgent requirements for, 37–38 validation in, 22–24 comparative studies of same molecule labeled in different positions in, 22–23, 23f comparison of labeled stereoisomers in, 23–24 Radiotracer/tracer kinetic models, renal, 662–667 See also Renal radiopharmaceuticals of chemical microspheres, 663f–665f, 664–666 (See also Chemical microspheres) of freely diffusible tracers, 662–664, 663f, 664b of glomerular filtration, 666 of radioligands, 666–667 types of, 662 use of, 662 Radiotracer/tracer models with multiple tissue compartments, compartmental modeling for, 87–91 18 for [ F]-FDG, 89–91, 90f overview, 87–88 volumes of distribution in, 88–89, 88f Ramp filter, 72 Random coincidences, 78–79, 79f Random events, 51 Rapid radiotracer chemistry, 16–21 carbon-11 and fluorine-18 production in, 16–18, 17f, 17t carbon-11 labeled compounds in, 18–20 fluorine-18 (18F)-labeled compounds in, 20–21, 20f time in, 16 [82Rb] washout kinetics, vs PET myocardial viability evaluation of ischemic cardiomyopathy, 581 Reactions per second (dn), Rebinning algorithms, for 3-D PET, 75–76 Receptors See also specific receptors as targets for PET drug development, 637 Recoil energy, Reconstruction algorithms, 70–74 filtered back-projection in, 71–73, 72f, 73f iterative reconstruction in, 73–74 projection data in, 70–71, 70f, 71f reduction in computational load in, 74 Reduction in computational load, in reconstruction algorithms, 74 Regional cerebral blood flow (rCBF), 480, 481, 481f Region of interest (ROI) consistency in, 108 on standardized uptake value, 107, 107f volumetric, 108 Registration intersubject, 102 intrasubject, intermodality, 100–102, 101f, 102f intrasubject, intramodality, 100 in PET/CT image fusion prospective “hardware,” 111–112 retrospective, 112 Reinnervation, myocardial neurotransmitter imaging of after heart transplantation, 614–615, 614f after myocardial infarction, 612 LWBL053-3787G-IND[713-730].qxd 8/16/08 1:23 AM Page 727 Aptara Inc Index Remodeling, angiotensin II receptor imaging of, 671–672 Renal See also Kidney entries Renal cancer, 379, 380f, 381f Renal protection, 671 Renal radiopharmaceuticals, 662 chemical microspheres, 663f–665f, 664–666 freely diffusible tracers, 662–664, 663f, 664b kinetic properties of, 661 88 [ Re]-perrhenate, 654 Reporter genes, nonsuicide, imaging gene expression with, 649–650, 649f Respiratory motion artifact, 66, 66f, 136f, 137 Respiratory muscles, [18F]-FDG distribution in, 141, 142f Resynchronization therapy, cardiac, PET myocardial perfusion evaluation of, 559 Retro-orbital metastasis of neuroendocrine carcinoma (CUP syndrome), [68Ga]DOTA-NOC/DOTA-TOC receptor PET/CT of, 427f RGD, 680–681, 681f Rhabdomyosarcoma, PET and PET/CT of in children, 457, 457f embryonal, in children, 450f Rheumatoid arthritis, FDG PET/CT of, 622 Rib fracture healing, [18F]-FDG uptake in, 154, 162f Right ventricular oxygen consumption, 601–602 Ring, PET, 48, 49f RIPTag model, 682 Ro-15-1788, [11C] ([11C]flumazenil), 30, 31f Rolipram, [11C], 34, 34f Rubidium-82 [82Rb] as myocardial blood flow tracer, 542, 542t, 543f production of, 10 Rubidium-82 [82Rb] chloride, renal PT imaging with, 663f–665f, 664–666 S Sacral insufficiency fracture, [18F]-FDG uptake in, 154, 163f Salivary gland malignancies of, 231, 232f physiologic FDG activity in, 222, 222f Sarcoidosis FDG PET/CT of, 627 [18F]-FDG uptake in, 163, 164f Sarcomas, PET and PET/CT of, 392–400 classification of, 392 for Ewing’s tumors, 398–399, 398t FDG PET as surrogate marker for drug treatment benefit in, 707–708 FMISO for imaging of, 400 for malignant bone tumors, 398, 398t for malignant cartilage tumors, 399–400, 399t for soft tissue sarcomas, 392–398 (See also Soft tissue sarcomas) Scanners CT, 60 multiple-row detector CT (MDCT), 60, 61f Scan parameters, in PET/CT, 63–64, 63f, 64t Scatter, in CT, 59 Scattered coincidence events, 79–80 Scattered events, 50, 51f Scatter fraction, 50 SCH23390, 26, 26f SCH39166, 26, 26f Schizophrenia, SPECT and PET of, 517–520 antipsychotic drug occupancy studies in, 519–520 dopamine transmission in, 517–519 prefrontal, 519 subcortical, 517–519, 518f ␥-aminobutyric acid secretion transmission in, 519 serotonin transmission in, 519 Selective serotonin reuptake inhibitors (SSRIs), occupancy studies of, 523 Semicarbazone complexes, for hypoxia imaging, 466–467 Semiquantitative image interpretation, in PET myocardial perfusion, 546, 547f, 548f Serotonin (5-HT), 28 ecstasy on, 528 receptors for (See 5-HT) Serotonin production pathway, radiopharmaceuticals based on, 418–419, 419f Serotonin synthesis imaging, 494 Serotonin system, brain, radiotracers for, 28–29, 28f, 29f Serotonin transmission in major depressive disorder, 520–523, 522f in personality disorders, 525 in schizophrenia, 519 Serotonin transporter (SERT) in cocaine abuse, 527 in major depressive disorder, 521–523, 522f radiotracers for, 29, 29f in schizophrenia, 519 SGLT transporter, 668 Shielding requirements, in PET/CT, 65 Short-lived positron emitters, physical properties of, 17, 17t Signal transduction pathways, radiotracers for, 33–34, 34f Silencing, gene, 655 Single-photon emission computed tomography (SPECT) See also specific disorders vs PET, 49 Single-row detector CT (SDCT), 60 Sinogram, projection, 71, 71f Skeletal muscle FDG uptake in, 449 [18F]-FDG distribution in, 140f, 141–142, 142f–144f Slice imaging, as series of 2-D images, 70 Small bowel, neuroendocrine carcinoma of, with metastases, [68Ga]-DOTA-NOC/DOTATOC receptor PET/CT of, 429f Small cell lung cancer (SCLC), 255, 255f [68Ga]-DOTA-NOC/DOTA-TOC receptor PET/CT of, 429, 432f paraneoplastic cerebellar degeneration in, 439 Smokers and smoking antioxidant therapy for, PET myocardial perfusion evaluation of, 557 in lung cancer, 248 MAO A and B in brain of, 27 molecular imaging of, 528–529 PET myocardial perfusion evaluation of, 557 Social phobia, 525 Sodium-hydrogen exchanger (NHE), 667–668 Sodium transporters, renal, 667–668 Soft tissue infections, focal, FDG PET of, 624–625 Soft tissue sarcomas classification of, 392, 393t core needle biopsy of, 392–393 distribution of, 392 Soft tissue sarcomas, PET and PET/CT of, 392–398 for diagnosis, 393–396, 394f–395f on patient outcome, 397–398 spatial heterogeneity in tumor uptake in, 392, 392f 727 for staging, 396, 396t for treatment response assessment, 396–397, 397f Soft tissue tumors, pediatric PET and PET/CT of, 457, 457f Solitary pulmonary nodules, 248–251 CT of, 248–249 evaluation of, 248–251, 249f, 250f tissue sampling in, 249 Solitary pulmonary nodules, PET and PET/CT of FDG PET/CT in, 249–251, 249f, 250f FDG PET in, 249, 249f, 250f multidetector CT with dynamic contrast enhancement in, 249–250 Somatostatin, 416 Somatostatin receptor affinity profiles of subtypes of, 417, 417t in normal organs/tissues, 416–417, 416t overexpression of, in malignant lymphoma, 266–267 radiopharmaceuticals based on expression of, 413, 416–418, 416t, 418f tumors with proven expression of, 417, 417t Somatostatin receptor family, in neuroendocrine tumors, 118 Somatostatin receptor proteins, 416 Somatostatin synthetic analogues, 418, 418f Sorafenib, 678 SPA-RQ, [18F], 36f, 37 Spatial resolution, 49 Specific activity, 4–5, 4t effective, 18 terms describing, 17–18 SPECT (single-photon emission computed tomography) See also specific disorders vs PET, 49 SPECT-MR image fusion in, 113–115, 114f mapping histology back to in vivo imaging in, 114–115, 114f Spinal cord tumors, 214–215, 214f Spinocerebellar atrophy, pre- and postsynaptic dopaminergic neurochemical imaging of, 487, 487t Squalamine, 678 11 (S,S)[ C]-MRB, 36, 36f Standardized uptake value (SUV), 55, 106–115, 171 body mass and size on, 108–109, 108f, 109f, 109t in children, 449–450 definition of, 106 in fluorothymidine PET, 109 formulas for calculation of, 108, 109t kinetic modeling approach challenges in, 106 Larson-Ginsberg index in, 108 in normal tissue, 107, 107f region of interest consistency on, 108 region of interest size on, 107, 107f reproducibility of, from study to study, 107–108 single maximal, 108 technical factors affecting, 109, 109t test/retest behavior of, 108 time from injection to imaging on, 107, 107f time to plateau of, 107 in treatment-response assessment, 109, 109t use of, 106 volumetric region of interest on, 108 Standardized uptake value lean body mass (SUV-LBM), 109, 109t Steele-Richardson-Olszewski syndrome, 485, 485f LWBL053-3787G-IND[713-730].qxd 8/16/08 1:23 AM Page 728 Aptara Inc 728 Index Stem cell therapy, cardiac, PET myocardial perfusion evaluation of, 559 Stereoisomers, labeled See also specific stereoisomers comparison of, 23–24 Stimulant-induced dopamine release, 526–527 Stomach, [18F]-FDG distribution in, 144, 147f Stress, exercise, PET myocardial perfusion evaluation of, 545–546 Stress FDG imaging, of myocardial viability, 581–582 Stress test, PET myocardial perfusion evaluation of dobutamine, 545 vasodilator, 545, 545f Stroke, CT and MRI in management of, 488 Stroke, PET and PET/CT of, 488–491 cerebral blood volume in, 488–489, 488t, 489t cerebral oxygen metabolism in, 488, 488t chronic arterial occlusive disease and hemodynamic reserve in, 489–490 hemorrhagic stroke, 490 ischemic acute, 489, 489t hemodynamic factors in, 489 subacute changes in, 489 multitracer PET for management in, 490 for neuronal and hypoxia imaging, 490–491 oxygen extraction fraction in, 488, 488t for prognosis estimation post-stroke, 490 Strontium/rubidium system, 10 Stunning, myocardial, 565–566 SU11248, 678 Submandibular glands normal [18F]-FDG uptake in, 139, 140f physiologic FDG activity in, 222, 222f Substance abuse, SPECT and PET of, 526–530 alcohol, 528–529 cocaine, 526–527 D2 receptors in, 526f ecstasy, 528 heroin, 528 methamphetamine, 527–528 nicotine, 528–529 Substance P, 37 Substance P radiotracers, 36f, 37 Substrate transport, 667 Suicide genes, 645, 646t, 648–649 Suicide gene therapy imaging of, 645, 646t on tumor vascularization, 646 SUL, 109, 109t Sunitinib, 403, 678 Suramin, 678 Sydenham chorea, 486 Symmetry in head and neck PET/CT, 231–234, 233f postsurgical, 231, 233f Sympathetic nerve terminal, 607–608, 608f Syndrome X, PET myocardial perfusion evaluation of, 558 Synovitis, FDG PET/CT of, 622 T Talc pleurodesis, 256, 256f Tamoxifen, estrogen-receptor blockage by, in PET drug development, 638–639, 638f Targets enriched in PET radionuclide production, shortage of, imaging of, 634–635 irradiation of, in PET radionuclides, 3–4 penetration of, anti-infective drug, PET assessment of, 635–636, 635f Target wall, on specific activity, 4–5 99m Tc-HYNIC-VEGF, 686 99m Tc-NC100692, 686 Teratoid/rhaboid tumor in children, PET of, 450–451, 451f Testicles, [18F]-FDG distribution in, 149, 152f Testicular cancer, 385–386, 386t TETA-octreotide, [64Cu], for neuroendocrine tumors, 433 Thalidomide, 678 Therapeutic hypothesis, imaging information and, 637–638 Therapy assessment See also specific disorders and therapies monitoring gene therapy via measurement of, 646–648, 647f PET myocardial perfusion in, 556, 559 d-threo-methylphenidate, [11C], 18, 26, 27f Thymic rebound, after chemotherapy in children, 448, 449f Thymidine, 639, 640f analogues of, 639, 640f [11C], 35, 35f monitoring tumor response with, 170–171 Thymidine analogue probes of tumor cell proliferation, in PET drug development, 639, 639f, 640f Thymidine (TdR)-FDG, 3-O-methylglucose, posttherapeutic accumulation of, 647 Thymus gland [18F]-FDG uptake in, 151, 156f [18F]-FDG uptake in children in, 448, 449f Thyroid cancer classification of, 240, 241f, 242f epidemiology of, 240 fine-needle aspiration of, 243–245 papillary metastatic, 240, 242f metastatic follicular variant of, 240, 241f Thyroid cancer, PET and PET/CT of, 240–245 alternative PET tracers in, 245 FDG PET in, 241–245 for anaplastic cancers, 245 for poorly differentiated forms, 245 thyroid stimulating hormone and, 243, 244f 68 [ Ga]-DOTA-NOC/DOTA-TOC receptor PET/CT in, 430f 123 131 I, I, and 99mTc in, 240 Thyroid gland [18F]-FDG distribution in, 149, 153f glucose metabolism in, 240–241 physiologic FDG activity in, 222, 223f Thyroiditis, [18F]-FDG uptake in, 149, 153f Thyroid nodule, [18F]-FDG uptake in, 149, 153f, 231 Thyroid-stimulating hormone, FDG PET imaging and, 243, 244f Thyroid transcription factors-1/2 (TTF1/TTF2), 651–652 Time of flight (TOF), for 3-D PET, 76–77 Time of flight (TOF) PET, 55–57, 56f Timing See also specific disorders of PET for monitoring treatment response, 169–170, 170t Timing window, 51 Tirapazamine (TPZ), 468–469 Tissue-specific transcriptional regulation, 651 Tissue time activity curves, measuring, 94, 94f Tissue vascular volume, 680 TNP-470, 678 Tomography computed (See CT (computed tomography)) as series of 2-D images, 70 Tongue, [18F]-FDG distribution in, 141–142, 144f Tonsils adenoid, [18F]-FDG uptake in, 151, 156f palatine [18F]-FDG distribution in, 153, 157f normal [18F]-FDG uptake in, 139, 140f Toxoplasmosis, FDG PET/CT of infection in, 627 Tracers See Radiopharmaceuticals Transcriptional regulation, tissue-specific, 651 Transforming growth factor- (TGF-), in kidneys, 671 Transitional cell carcinoma of urinary bladder, 380–385 See also Bladder cancer Transplant See specific organs Transport, substrate, 667 Transporters, 667 See also specific transporters ATP binding cassette transporter family, 667 dopamine (DAT), 518–519, 527–528 glucose (GLUT), 119, 565, 668 overexpression of, in cancer, 119–120, 120f, 367 renal, 668 human norepinephrine transporter (hNET), 654 norepinephrine (NET) in neuroblastoma, pheochromocytoma, and neuroendocrine tumors, 118 radiotracers for, 36, 36f organic anion, 667 organic cation, 667 renal, 667–668 serotonin (SERT), 29, 29f, 519, 521–523, 522f, 527 SGLT, 668 sodium, renal, 667–668 vesicular, and dopamine, 26–27, 27f vesicular mono(amine) (VMAT2), 27 Treatment response monitoring See Monitoring treatment response Tremor, essential, 486 Tricarboxylic acid (TCA) cycle, 590–591, 590f Tritium blood flow quantification, [13N], 548 Truncal muscles, [18F]-FDG distribution in, 141, 142f Tubular transport, as indicator of renal function, 666 Tumor/background ratios, time on, 107 Tumor cell proliferation, thymidine analogue probe of, in PET drug development, 639, 639f, 640f Tumor delivery of drugs, PET assessment of, 636, 636f Tumor lesions, [68Ga]-DOTA-NOC/DOTA-TOC receptor PET/CT of, 426, 427f Tumor measurement quantitation, PET, 171–172 Two-shoot method, Tyrosine kinase inhibitors, 678 U Upper abdominal metastases, [68Ga]-DOTANOC/DOTA-TOC receptor PET/CT of, 426, 429 Uptake-2-system, 608 Uptake value, standardized See Standardized uptake value (SUV) Uterine cancer patient preparation and imaging of, 348 Uterus, [18F]-FDG distribution in, 149, 151f V Valvular heart disease, PET myocardial perfusion evaluation of, 558 Vascular endothelial growth factor (VEGF) receptors, imaging of, 686 LWBL053-3787G-IND[713-730].qxd 8/16/08 1:23 AM Page 729 Aptara Inc Index Vascular endothelial growth factors (VEGFs), imaging of, 686 Vascular grafts [18F]-FDG uptake in, 154, 160f infection of, FDG PET/CT of, 625, 626f Vascular infection and inflammation, FDG PET/CT of, 625–626 atherosclerotic plaque, vulnerable, 625–626 vascular graft infection, 625, 626f vasculitis, 625 Vascular permeability, imaging in assessment of, 680 Vasculitis, FDG PET/CT of, 625 Vasoactive intestinal peptide (VIP), radiopharmaceuticals based on, 420, 420t Vasodilator stress test, PET myocardial perfusion evaluation of, 545, 545f Ventricular arrhythmia, myocardial neurotransmitter imaging of, 612–613 Verner Morrison syndrome, 412 Vertebral body compression fractures, [18F]-FDG uptake in, 151, 155f Vertebral fracture, [18F]-FDG uptake in, 154, 155f Vesicles, adrenergic neuron, 608 Vesicular mono(amine) transporters (VMAT2), 27 Vesicular transporters, dopamine and, 26–27, 27f Viral vector biodistribution, 644–645 Vitaxin, 678 Vocal cords, physiologic FDG distribution in, 223, 225f Vocalization muscles, [18F]-FDG distribution in, 141, 143f Volume of distribution (VD) in blood flow imaging, 679 for multicompartment models, 88–89, 88f Volume transfer constant (Ktrans), 680 Volumetric region of interest, 108 Voxel, in CT, 59 729 W Waldenström’s macroglobulinemia, 267 Waldeyer’s ring, 223 Warthin tumors of parotid gland, 231, 232f [18F]-FDG uptake in, 154, 159f Wernicke’s region, 481 West syndrome, 492–493 Wilms’ tumor, pediatric PET and PET/CT of, 454, 455f Work metabolic index (WMI), 598 Wound healing, [18F]-FDG uptake in, 154, 159f X Xanthoastrocytoma, pleomorphic, 213, 214f X-ray imaging, 2-D nature of, 69–70 Z Zinc-62 (62Zn), production routes for, Z-score maps, of FDG PET of dementia, 509, 513f ... [ 123 I]-IMP, iodine- 123 N-isopropylp-iodoamphetamine LWBK053-3787G-9. 02[ 500-515].qxd 5 02 15/8/08 5:34 PM Page 5 02 Aptara Inc Principles and Practice of PET and PET/ CT Brain PET Tracer: [18F] -2- fluoro -2- deoxy-D-glucose... LWBK053-3787G-9.01[479-499].qxd 14-08 -20 08 05:56 PM Page 4 82 Aptara Inc 4 82 Principles and Practice of PET and PET/ CT increase of synaptic activities in the thalamus, possibly as a consequence of improved corticothalamic...LWBK053-3787G-9.01[479-499].qxd 14-08 -20 08 05:56 PM Page 480 Aptara Inc 480 Principles and Practice of PET and PET/ CT Imaging of resting glucose metabolism and/ or blood flow in the brain represent