Theoretical assessment of specific radioactivity the effect of target burn up, isotope dilution and target purity and the application for lu 177 production

Conference Presentation 4th Asia-Pacific Symposium on Radiochemistry ’09 November 29 – December 4, 2009 Napa Valley, California, U.S.A Introduction - Advanced nuclear medicine ( PET & SPECT molecular imaging and targeted radiotherapy) needs very high specific activity (SA) radioisotopes for peptide vectors & Mab-based radiopharmaceutical preparation, e.g.177Lu SA > 20 Ci/ mg -The reactor-based radioisotope production advantage lies in its large production capacity, comfortable targetry and robustness However, the specific activity is a subject to be concerned - SA assessment becomes a lot more serious than reaction yield which is a conventional concern for radioisotope producers In this report -Theoretical approach to SA assessment with widely used nuclear reactions reported together with an up-to-date application for the 177Lu radioisotope production -SA assessment result is served as an effective tool for optimization and quality assurance for production process Theoretical approaches Reactor based radioisotope production Conventional concerns: - Neuron capture reactions - Reaction yield assessment vs Cross section & Neutron flux Present issues and requirements: -Very high specific radioactivity radioisotope & reasonable reaction yield -Very high cross section (n,γ) reaction or radioactive transformation Problem Target composition: Target nuclide and Isotopic & elemental impurities Yield build-up Specific radioactivity Target burn-up Unwanted nuclear reactions Neutron parameters & characteristics Activation and post-irradiation time - SA assessment makes the interactions between parameters observable for optimization and quality assurance purposes - SA assessment approaches formulated in mathematical equations to get the highest standardization Three main nuclear reactions for reactor based radioisotope production Ri,A Complex Target System: Sg, A For higher SA radioisotope production S1,A S2,A; Sg,A; …Sn,A Ri,A Simple Target System: For lower SA radioisotope production Simple Target System: For lower SA radioisotope production Target nuclide Impure nuclides (Isotopic) Ri,A S2,A Sg,A Sn,A Un-burned atom numbers of Sg,A Burned-up atom numbers of Sg,A N S g , A = N , S g , A e Nb,S g , A = N 0, S g , A (1 − e Maximum Reaction yield of Sg,Afor Ri − ∆ S g , A tirr ) T1/ 2− B = 0.693/ ∆S1, A Half Burn-up Time of Sg,A Reaction yield of Sg,Afor Ri − ∆ S g , A t irr NRi = No,S1, A φth.Ω1,i ΛRi − ∆S1, A N Ri − max = −∆S1, A tirr (e N o , S1, A φ th Ω 1, i Λ R i − ∆ S1 , A −e −ΛRi tirr ) (e − p − e − h ) Specific Radioactivity (SA) in Simple Target System SA of Ri radioisotope in simple multi-isotope target system, with SAmax SARi ,tirr = 100.N Ri /(NRi + N0,S1, A e − ∆S1, A tirr + N0,S2, A e − ∆S2 , A tirr + + N0,Sg , A e − ∆S g , A tirr ) SA of Ri radioisotope in simple two-isotope target system, with SAmax m= j −∆S1, A tirr 100.(e SARi ,tc = −ΛRi tirr −e −tc ∑ λm, Ri ).e m=1 m= j (e −∆S1, A tirr −ΛRi tirr −e ).e −tc ∑ λm, Ri m=1 −∆S1, A tirr + ((ΛRi − ∆S1, A ) /φth.Ω1,i ).e −∆S2, A tirr + b.(P2 / P1 ).e SA of Ri radioisotope in simple one-isotope target system, SARi ,tirr = 100× (1 − e − ( Λ Ri + ∆ S1, A ).tirr ) /(a − e − ( Λ Ri + ∆ S1, A ).tirr ) No maximum SA Maximum SA of Ri radioisotope in simple target system If the differential of SARi d ( SA dt −∆S1, A tirr,SAmax (∆S1,A e −∆S1, A tirr,SAmax (e −ΛRi tirr,SAmax −ΛRi e −ΛRi tirr,SAmax −e i ,t ) irr = irr −ΛRi tirr,SAmax ).(e −ΛRi tirr,SAmax ).(ΛRi e R −∆S1, A tirr,SAmax −a.e −∆S1, A tirr,SAmax −∆S1,A a.e −∆S2, A tirr,SAmax −b.(P2 / P1).e )− −∆S2, A tirr,SAmax −∆S2,A b.(P2 / P1).e ) =0 SA of 177 Lu in 176/ 175 Lu target ( A typical 2- isotope target system) 100% 176Lu 74%176Lu + 26%175Lu 74%176Lu + 26%175Lu tY tSA 99.9 % 176Lu 99.9 % 176Lu tSA/ tY 95% 50% Φ=3.1014 50% 176Lu Complex Target System: For higher SA radioisotope production Radioactive source S1 Target nuclide Ri,A -Atom number NSg,A -Atom number N1,Ri Sg,A Impure nuclides (Isotopic) -Specific activity SA1,Ri Radioactive source S2 Ri,A Impure nuclides (Elemental) Atom number N2,Ri -Specific activity SA2,Ri S2,A; Sg,A; …Sn,A N S g , A ,t c = N o , S , B φ th Ω , y ( Λ R y − ∆ S , B ) Λ R y ∆ S , B × − Λ R y tirr  (λ  λ λ Λ − ∆ ) + ( ∆ − Λ ∆ ) e − R → S R R → S S R → S S R S   y g ,A y y g ,A ,B y g ,A ,B y ,B  − Λ t −λ t   ( λ R → S Λ R − Λ R ∆ S ).e − ∆ S , B tirr − Λ R ∆ S ( e − ∆ S , B tirr − e R y irr ).e R y → S g , A c  y g ,A y y ,B y ,B   m= j NRi,tc For source S2 SA − ∑ λm,Ri tc e−d1.tirr e−d2.tirr e−d3.tirr = N0,S1,B f2 f3.[ + + ].e m=1 (d2 − d1)(d3 − d1) (d1 − d2 )(d3 − d2 ) (d1 − d3)(d2 − d3) R i ,tc = 100 × N R i ,tc × (N R i ,tc + N S g ,A ,t c ) m= j For source S1 100.(e SARi ,tc = SA of the mixture of radioactive sources, SAMix,Ri −∆S1, A tirr −e −ΛRi tirr ).e −tc ∑ λm, Ri m=1 m= j (e −∆ S1, A tirr −e −ΛRi tirr ).e −tc ∑ λm, Ri m=1 + ((Λ Ri − ∆ S1, A ) / φth Ω1,i ).e j =n j =n j =n k =n j =1 j =1 j =1 k =1 −∆ S1, A tirr + b.(Pimp, A / P1 ) SAMix, Ri = (∏ SAj ,Ri × ∑ Aj , Ri ) /(∑ ( Aj , Ri × ∏ SAk ,Ri )) with j ≠ k SA of 177 Lu in 176/ 175 Yb target ( A typical multi- isotope target system) Nuclear characteristics of radionuclides produced in 176Yb target matrix [3] ( * Elemental Lu content being of natural isotopic abundance in 176Yb target is assumed as 97.41 % 175Lu and 2.59 % 176Lu) SA of 177 Lu in 176/ 175 Yb target ( A typical multi- isotope target system) Impurity-free 176Yb target 99.995%176Yb + 50 ppm Lu 98%176Yb + 2% 174Yb 97.995%176Yb + 2% 174Yb+ 50 ppm Lu 150 A: B: C: D: SA of 177Lu radioisotope in the 176 Yb target vs irradiation time and content of 174Yb- and elemental Lu- impurities SA of 177Lu isotope in impurity-free 176Yb target SA of 177Lu isotope in the 176Yb target containing 1.93% 174Yb SA of 177Lu isotope in the 176Yb target containing 50 p.p.m Lu impurities SA of 177Lu isotope in the 176Yb target containing 1.93% 174Yb and 50 p.p.m Lu impurity Impurity-free 176Yb target 98%176Yb + 2% 174Yb 99.995%176Yb + 50 ppm Lu 97.995%176Yb + 2% 174Yb+ 50 ppm Lu SA of 177Lu radioisotope in the 176 Yb target vs post-irradiation time and content of 174Yb and Lu impurities Thermal neutron flux: 5.1013 n.cm-2.s-1, ; Irradiation time: 200 hours A: SA of 177Lu isotope in the impurity-free 176Yb target B: SA of 177Lu isotope in the 176Yb target containing 1.93% 174Yb C: SA of 177Lu isotope in the 176Yb target containing 50 p.p.m Lu impurities D: SA of 177Lu isotope in the target containing 1.93% 174Yb and 50 p.p.m Lu impurity (*) is the experimental measurement result for this type of target Conclusion SA assessment methods have been established and equations formulated for SA calculation of different target systems SA assessment method makes the interactions of interfering parameters evaluable SA assessment results are useful for the feasibility study of production capability of existing irradiation facility and targetry SA assessment is an effective tool for optimization and quality assurance in the radioisotope production Radioisotope Development Facilities • Nuclear Reactor at Lucas Heights – HIFAR (10MW) in operation since 1958 – OPAL (20 MW) inauguration in 2008 • Low Enriched Uranium (LEU) • National Medical Cyclotron (NMC) – – – – Based at Camperdown Commissioned in 1992 30 MeV from IBA Versatile: Production & Research • Further investment in Automation • Full GMP Facilities New OPAL reactor core Large Volume Irradiation Facilities Irradiation RIGs Storage Rack for Irradiation Facilities Pneumatic Transfer System Tubes Storage Rack for Irradiation Facilities Bulk Irradiation Facilities Hot Labs 176Lu /176Yb target irradiation can Automated separation of 177Lu from 176Yb target View publication stats ... =0 SA of 177 Lu in 176/ 175 Lu target ( A typical 2- isotope target system) SA of 177 Lu in 176/ 175 Lu target ( A typical 2- isotope target system) 100% 17 6Lu 74%17 6Lu + 26%17 5Lu 74%17 6Lu + 26%17 5Lu. .. ppm Lu 150 A: B: C: D: SA of 17 7Lu radioisotope in the 176 Yb target vs irradiation time and content of 174Yb- and elemental Lu- impurities SA of 17 7Lu isotope in impurity-free 176Yb target SA of. .. target SA of 17 7Lu isotope in the 176Yb target containing 1.93% 174Yb SA of 17 7Lu isotope in the 176Yb target containing 50 p.p.m Lu impurities SA of 17 7Lu isotope in the 176Yb target containing