Copyright © National Academy of Sciences. All rights reserved. Medical Isotope Production Without Highly Enriched Uranium http://www.nap.edu/catalog/12569.html Committee on Medical Isotope Production Without Highly Enriched Uranium Nuclear and Radiation Studies Board Division of Earth and Life Studies Copyright © National Academy of Sciences. All rights reserved. Medical Isotope Production Without Highly Enriched Uranium http://www.nap.edu/catalog/12569.html THE NATIONAL ACADEMIES PRESS 500 Fifth Street, N.W. Washington, DC 20001 NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committee respon- sible for the report were chosen for their special competences and with regard for appropriate balance. This study was supported by Contract/Grant No. DE-AM01-04PI45013 between the National Academy of Sciences and the U.S. Department of Energy. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the views of the organizations or agencies that provided support for the project. International Standard Book Number-13: 978-0-309-13039-4 International Standard Book Number-10: 0-309-13039-5 Cover: Image generated from a brain perfusion scan using technetium-99m (cour- tesy of Satoshi Minoshima, University of Washington). Overlay: Photograph of the University of Missouri Research Reactor (MURR) core (courtesy of the University of Missouri). Additional copies of this report are available from the National Academies Press, 500 Fifth Street, N.W., Lockbox 285, Washington, DC 20055; (800) 624-6242 or (202) 334-3313 (in the Washington metropolitan area); Internet, http://www.nap. edu. Copyright 2009 by the National Academy of Sciences. All rights reserved. Printed in the United States of America Copyright © National Academy of Sciences. All rights reserved. Medical Isotope Production Without Highly Enriched Uranium http://www.nap.edu/catalog/12569.html The National Academy of Sciences is a private, nonprofit, self-perpetuating society of distinguished scholars engaged in scientific and engineering research, dedicated to the furtherance of science and technology and to their use for the general welfare. Upon the authority of the charter granted to it by the Congress in 1863, the Acad- emy has a mandate that requires it to advise the federal government on scientific and technical matters. Dr. Ralph J. Cicerone is president of the National Academy of Sciences. The National Academy of Engineering was established in 1964, under the charter of the National Academy of Sciences, as a parallel organization of outstanding engi- neers. It is autonomous in its administration and in the selection of its members, sharing with the National Academy of Sciences the responsibility for advising the federal government. The National Academy of Engineering also sponsors engineer- ing programs aimed at meeting national needs, encourages education and research, and recognizes the superior achievements of engineers. Dr. Charles M. Vest is presi- dent of the National Academy of Engineering. The Institute of Medicine was established in 1970 by the National Academy of Sciences to secure the services of eminent members of appropriate professions in the examination of policy matters pertaining to the health of the public. The Insti- tute acts under the responsibility given to the National Academy of Sciences by its congressional charter to be an adviser to the federal government and, upon its own initiative, to identify issues of medical care, research, and education. Dr. Harvey V. Fineberg is president of the Institute of Medicine. The National Research Council was organized by the National Academy of Sciences in 1916 to associate the broad community of science and technology with the Academy’s purposes of furthering knowledge and advising the federal government. Functioning in accordance with general policies determined by the Academy, the Council has become the principal operating agency of both the National Academy of Sciences and the National Academy of Engineering in providing services to the government, the public, and the scientific and engineering communities. The Council is administered jointly by both Academies and the Institute of Medicine. Dr. Ralph J. Cicerone and Dr. Charles M. Vest are chair and vice chair, respectively, of the National Research Council. www.national-academies.org Copyright © National Academy of Sciences. All rights reserved. Medical Isotope Production Without Highly Enriched Uranium http://www.nap.edu/catalog/12569.html Copyright © National Academy of Sciences. All rights reserved. Medical Isotope Production Without Highly Enriched Uranium http://www.nap.edu/catalog/12569.html v COMMITTEE ON MEDICAL ISOTOPE PRODUCTION WITHOUT HIGHLY ENRICHED URANIUM CHRIS WHIPPLE (Chair), ENVIRON International Corporation, Emeryville, California STEVE M. LARSON (Vice Chair), Memorial Sloan-Kettering Cancer Center, New York, New York CYNTHIA ATKINS-DUFFIN, Lawrence Livermore National Laboratory, Livermore, California ANTHONY E. BOARDMAN, University of British Columbia, Vancouver D. JEFFREY BOSTOCK, Lockheed Martin Energy Systems (retired), Seabrook Island, South Carolina G. BRIAN ESTES, U.S. Navy (retired), Williamsburg, Virginia MILTON LEVENSON, Bechtel International (retired vice president), Menlo Park, California IRVIN W. OSBORNE-LEE, Prairie View A&M University, Prairie View, Texas EUGENE J. PETERSON, Los Alamos National Laboratory, Los Alamos, New Mexico RICHARD C. REBA, Georgetown University, Washington, DC, and the National Institutes of Health, Bethesda, Maryland IAIN G. RITCHIE, International Atomic Energy Agency (retired), Victoria, British Columbia THOMAS J. RUTH, TRI-University Meson Facility, Vancouver, British Columbia JASMINA VUJIC, University of California, Berkeley RAYMOND G. WYMER, Oak Ridge National Laboratory (retired), Oak Ridge, Tennessee Staff KEVIN D. CROWLEY, Study Director NAOKO ISHIBE, Program Officer DANIELA STRICKLIN, Program Officer COURTNEY GIBBS, Senior Program Assistant SHAUNTEÉ WHETSTONE, Senior Program Assistant Copyright © National Academy of Sciences. All rights reserved. Medical Isotope Production Without Highly Enriched Uranium http://www.nap.edu/catalog/12569.html vi NUCLEAR AND RADIATION STUDIES BOARD RICHARD A. MESERVE (Chair), Carnegie Institution, Washington, DC S. JAMES ADELSTEIN (Vice Chair), Harvard Medical School, Boston, Massachusetts JOONHONG AHN, University of California, Berkeley JOEL S. BEDFORD, Colorado State University, Fort Collins SUE B. CLARK, Washington State University, Pullman ALLEN G. CROFF, Oak Ridge National Laboratory (retired), St. Augustine, Florida PATRICIA J. CULLIGAN, Columbia University, New York, New York SARAH C. DARBY, Clinical Trial Service Unit, Oxford, United Kingdom JAY DAVIS, Lawrence Livermore National Laboratory (retired), Livermore, California ROGER L. HAGENGRUBER, University of New Mexico, Albuquerque DAVID G. HOEL, Medical University of South Carolina, Charleston HEDVIG HRICAK, Memorial Sloan-Kettering Cancer Center, New York, New York THOMAS H. ISAACS, Lawrence Livermore National Laboratory, Livermore, California PAUL A. LOCKE, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland BORIS F. MYASOEDOV, Russian Academy of Sciences, Moscow JOHN C. VILLFORTH, Food and Drug Law Institute (retired), Gaithersburg, Maryland RAYMOND G. WYMER, Oak Ridge National Laboratory (retired), Oak Ridge, Tennessee PAUL L. ZIEMER, Purdue University (retired), West Lafayette, Indiana Staff KEVIN D. CROWLEY, Director MICAH D. LOWENTHAL, Senior Program Officer JOHN R. WILEY, Senior Program Officer DANIELA STRICKLIN, Program Officer TONI GREENLEAF, Administrative and Financial Associate LAURA D. LLANOS, Administrative and Financial Associate MANDI M. BOYKIN, Senior Program Assistant SHAUNTEÉ WHETSTONE, Senior Program Assistant JAMES YATES, JR., Office Assistant Copyright © National Academy of Sciences. All rights reserved. Medical Isotope Production Without Highly Enriched Uranium http://www.nap.edu/catalog/12569.html vii Preface T his study was motivated by a conflict between the nonproliferation objectives of the Energy Policy Act of 1992, which created increas- ing pressures to phase out U.S. exports of highly enriched uranium (HEU) for medical isotope production, and the Energy Policy Act of 2005, which sought to increase the reliability of medical isotope supply by lift- ing the requirements of the 1992 Act for HEU exports to Canada, the Netherlands, Belgium, France, and Germany for medical isotope produc- tion. 1 At no time during the study were these dual objectives of securing HEU and providing a reliable supply of medical isotopes questioned by the committee—both objectives are obviously important. The question we pursued was the feasibility of achieving both. All of the U.S. supply of the most widely used medical isotope, technetium-99m (Tc-99m), is produced by irradiating HEU targets in a reactor, extracting molybdenum-99 (Mo-99) from the targets, and col- lecting the Tc-99m that is produced when Mo-99 decays. No Mo-99 is currently produced domestically for medical use. The two main sources of Mo-99 for use in the United States are the National Research Universal (NRU) Reactor operated by Atomic Energy of Canada, Ltd. (AECL) at its Chalk River, Ontario, site and the High Flux Reactor (HFR) operated by the Nuclear Research and Consultancy Group at the Petten, Netherlands, site. Both reactors are over 40 years old. 1 See Sidebar 1.3 for a discussion of these congressional amendments. Copyright © National Academy of Sciences. All rights reserved. Medical Isotope Production Without Highly Enriched Uranium http://www.nap.edu/catalog/12569.html viii PREFACE The Committee was tasked with evaluating the feasibility of converting medical isotope production of Mo-99 from HEU to low enriched uranium (LEU). For reasons discussed in Chapter 3, the report focuses on the feasi- bility of producing Mo-99 with LEU. In Section 630 of the Energy Policy Act of 2005, Congress defines feasibility to include consideration of cost, specifically, that “the average anticipated total cost increase from produc- tion of medical isotopes in such facilities without use of highly enriched uranium is less than 10 percent.” That Mo-99 can be produced in a reactor without using HEU is not in doubt; Argentina has been producing Mo-99 with an all-LEU system since 2002. An Argentine-designed and built reactor near Sydney, Australia, will likely produce Mo-99 with LEU fuel and targets in the near future, and an Argentine company is completing construction of a Mo-99 processing facility at an all-LEU reactor near Cairo, Egypt. As the committee began to assess the technology of isotope production and the system of production and distribution, it quickly came to under- stand that the system that supplies and distributes medical isotopes involves more than just cost considerations. We found that the medical community that uses Tc-99m and the industry that provides it greatly value the reli- ability of supply. During the study, there were three significant medical isotope outages in the United States and one currently ongoing in Europe. The first, from November 2005 through April 2006, was the result of a Tc-99m genera- tor supply disruption when a U.S based technetium generator producer, Mallinckrodt, shut down production because of a product recall. The second outage was the result of a safety-related shutdown of the NRU Reactor in Canada that began in late November 2007 and lasted about a month. The third outage was the result of the shutdown of HFR in the Netherlands that began in August 2008 and is expected to last through the middle of Febru- ary 2009. At about the same time, a Mo-99 processing facility in Belgium was also shut down after radioactive iodine was inadvertently vented to the environment. The global production of Mo-99 was inadequate to meet demand during these outages, and some hospitals and clinics were forced to postpone or cancel diagnostic imaging procedures. At the time of our study’s first meeting in February 2007, AECL was working to complete two new reactors, Maple I and Maple II, which were to be dedicated to medical isotope production, and a new Mo-99 process- ing facility. The reactors and their associated processing facilities would have had the capacity to supply essentially all of the Mo-99 needed to meet worldwide demand if necessary and would have provided redundancy to ensure reliability. However, for reasons described in Chapter 10, AECL discontinued work on the Maple reactors in May 2008. Planning is underway in Europe for a replacement for HFR in the Netherlands, but construction has not begun. Construction of a new Copyright © National Academy of Sciences. All rights reserved. Medical Isotope Production Without Highly Enriched Uranium http://www.nap.edu/catalog/12569.html PREFACE ix research reactor, the Jules Horowitz, has just begun in France, and it is scheduled to begin operation in 2014. As discussed in Chapter 3, other supplies could come online that could contribute to U.S. Mo-99 supply, including supplies from domestic producers. The supply of Mo-99 in the United States is likely to be unreliable until newer production sources come online. The reliability of the current supply system is an important medical isotope concern; as noted in Chapter 10, the committee has concluded that achieving a cost difference of less than 10 percent in facilities that will need to convert from HEU- to LEU-based Mo-99 production is much less important than is reliability of supply. Chris Whipple, Chair Steve Larson, Vice Chair Copyright © National Academy of Sciences. All rights reserved. Medical Isotope Production Without Highly Enriched Uranium http://www.nap.edu/catalog/12569.html [...]... 109-58 isotopes are a class of radioactive isotopes (radioisotopes) that have unstable nuclei and emit radiation This radiation is used for medical imaging and treatment A report of the Medical Copyright © National Academy of Sciences All rights reserved Medical Isotope Production Without Highly Enriched Uranium http://www.nap.edu/catalog/12569.html MEDICAL ISOTOPE PRODUCTION WITHOUT HIGHLY ENRICHED. .. Copyright © National Academy of Sciences All rights reserved Medical Isotope Production Without Highly Enriched Uranium http://www.nap.edu/catalog/12569.html 14 MEDICAL ISOTOPE PRODUCTION WITHOUT HIGHLY ENRICHED URANIUM committee held four meetings to receive information from subject matter experts, representatives of the medical isotope production and user communities, and congressional and federal... Sciences All rights reserved Medical Isotope Production Without Highly Enriched Uranium http://www.nap.edu/catalog/12569.html 10 MEDICAL ISOTOPE PRODUCTION WITHOUT HIGHLY ENRICHED URANIUM tration [DOE-NNSA]), it was jointly agreed that the following task would also be included as part of this study: If the National Academies determine that the procurement of medical isotopes from commercial sources... separated Mo-99, which is con For example Russian English Venture in Isotope Supply Services (REVISS) sells Russianproduced isotopes Copyright © National Academy of Sciences All rights reserved Medical Isotope Production Without Highly Enriched Uranium http://www.nap.edu/catalog/12569.html 18 MEDICAL ISOTOPE PRODUCTION WITHOUT HIGHLY ENRICHED URANIUM tained in a solution, is then adsorbed onto an alumina... Academy of Sciences All rights reserved Medical Isotope Production Without Highly Enriched Uranium http://www.nap.edu/catalog/12569.html MEDICAL ISOTOPE PRODUCTION WITHOUT HIGHLY ENRICHED URANIUM to share R&D costs with existing and potential new producers that could supply the U.S market as a means to incentivize the conversion process and encourage new domestic production Remove disincentives to conversion... reserved Medical Isotope Production Without Highly Enriched Uranium http://www.nap.edu/catalog/12569.html Summary T his report is the product of a congressionally mandated study to examine the feasibility of eliminating the use of highly enriched uranium (HEU) in reactor fuel, reactor targets, and medical isotope production facilities The report focuses primarily on the use of HEU for the production. .. HEU is uranium enriched in uranium- 235 (U-235) to concentrations greater than or equal to 20 weight percent Uranium enriched in U-235 to concentrations less than 20 weight percent is low enriched uranium (LEU); see Sidebar 1.1 The “m” denotes that this radionuclide is metastable Copyright © National Academy of Sciences All rights reserved Medical Isotope Production Without Highly Enriched Uranium. .. even if they have a unique fuel design or a defense mission The Copyright © National Academy of Sciences All rights reserved Medical Isotope Production Without Highly Enriched Uranium http://www.nap.edu/catalog/12569.html MEDICAL ISOTOPE PRODUCTION WITHOUT HIGHLY ENRICHED URANIUM committee recommends that DOE-NNSA, in cooperation with the International Atomic Energy Agency (IAEA), make an effort... this report Chris Whipple, Chair Copyright © National Academy of Sciences All rights reserved Medical Isotope Production Without Highly Enriched Uranium http://www.nap.edu/catalog/12569.html Copyright © National Academy of Sciences All rights reserved Medical Isotope Production Without Highly Enriched Uranium http://www.nap.edu/catalog/12569.html Reviewers T his report has been reviewed in draft... http://www.nap.edu/catalog/12569.html 12 MEDICAL ISOTOPE PRODUCTION WITHOUT HIGHLY ENRICHED URANIUM SIDEBAR 1.3 Congressional Actions on HEU Use for Medical Isotope Production U.S congressional efforts to reduce the use of HEU for isotope production date from the early 1990s The Energy Policy Act of 1992 (the 1992 Act) required that foreign producers who received HEU from the United States cooperate in converting to LEU-based production . rights reserved. Medical Isotope Production Without Highly Enriched Uranium http://www.nap.edu/catalog/12569.html Committee on Medical Isotope Production Without Highly Enriched Uranium Nuclear. reserved. Medical Isotope Production Without Highly Enriched Uranium http://www.nap.edu/catalog/12569.html Copyright © National Academy of Sciences. All rights reserved. Medical Isotope Production Without. Isotope Production Without Highly Enriched Uranium http://www.nap.edu/catalog/12569.html Copyright © National Academy of Sciences. All rights reserved. Medical Isotope Production Without Highly Enriched