Molybdenum-99 for Medical Imaging Molybdenum-99 for Medical Imaging Committee on State of Molybdenum-99 Production and Utilization and Progress Toward Eliminating Use of Highly Enriched Uranium Nuclear and Radiation Studies Board Division on Earth and Life Studies A Report of Copyright © National Academy of Sciences. All rights reserved. Molybdenum-99 for Medical Imaging THE NATIONAL ACADEMIES PRESS 500 Fifth Street, NW Washington, DC 20001 This activity was supported by Grant No. DE-PI0000010/DE-DT0007382 between the National Academy of Sciences and the U.S. Department of Energy, National Nuclear Security Administration. Any opinions, findings, conclusions, or recom- mendations expressed in this publication do not necessarily reflect the views of any organization or agency that provided support for the project. International Standard Book Number-13: 978-0-309-44531-3 International Standard Book Number-10: 0-309-44531-0 Digital Object Identifier: 10.17226/23563 Cover: Technetium-99m, the decay product of molybdenum-99, is the most widely used radionuclide for medical imaging. The images on the cover were produced during a myocardial perfusion imaging (MPI) study using technetium-99m to assess blood flow to heart tissues (courtesy of Henry D. Royal, Washington University School of Medicine). The series of tomographic images at the top are produced during the stress portion (either exercise or pharmacological) of the test and the images at the bottom during the rest portion. The center image (referred to as a bulls-eye image) combines multiple images taken at stress or rest (in this case at rest) to assess myocardial perfusion defects. The black area of the bulls-eye image corresponds to areas of abnormal myocardial perfusion. The patient was diagnosed with a myocardial infarction (i.e., heart attack). Additional copies of this publication are available for sale from the National Acad- emies Press, 500 Fifth Street, NW, Keck 360, Washington, DC 20001; (800) 624- 6242 or (202) 334-3313; http://www.nap.edu. Copyright 2016 by the National Academy of Sciences. All rights reserved. Printed in the United States of America Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2016. Molybdenum-99 for Medical Imaging. Washington, DC: The National Acad- emies Press. doi: 10.17226/23563. Copyright © National Academy of Sciences. All rights reserved. Molybdenum-99 for Medical Imaging The National Academy of Sciences was established in 1863 by an Act of Congress, signed by President Lincoln, as a private, nongovernmental institution to advise the nation on issues related to science and technology. Members are elected by their peers for outstanding contributions to research. Dr. Marcia McNutt is president. The National Academy of Engineering was established in 1964 under the charter of the National Academy of Sciences to bring the practices of engineering to advising the nation. Members are elected by their peers for extraordinary contri- butions to engineering. Dr. C. D. Mote, Jr., is president. The National Academy of Medicine (formerly the Institute of Medicine) was established in 1970 under the charter of the National Academy of Sciences to advise the nation on medical and health issues. Members are elected by their peers for distinguished contributions to medicine and health. Dr. Victor J. Dzau is president. The three Academies work together as the National Academies of Sciences, Engi- neering, and Medicine to provide independent, objective analysis and advice to the nation and conduct other activities to solve complex problems and inform public policy decisions. The Academies also encourage education and research, recognize outstanding contributions to knowledge, and increase public under- standing in matters of science, engineering, and medicine. Learn more about the National Academies of Sciences, Engineering, and Medicine at www.national-academies.org. Copyright © National Academy of Sciences. All rights reserved. Molybdenum-99 for Medical Imaging Reports document the evidence-based consensus of an authoring committee of experts. Reports typically include findings, conclusions, and recommendations based on information gathered by the committee and committee deliberations. Reports are peer reviewed and are approved by the National Academies of Sciences, Engineering, and Medicine. Proceedings chronicle the presentations and discussions at a workshop, sym- posium, or other convening event. The statements and opinions contained in proceedings are those of the participants and have not been endorsed by other participants, the planning committee, or the National Academies of Sciences, Engineering, and Medicine. For information about other products and activities of the Academies, please visit nationalacademies.org/whatwedo. Copyright © National Academy of Sciences. All rights reserved. Molybdenum-99 for Medical Imaging COMMITTEE ON STATE OF MOLYBDENUM-99 PRODUCTION AND UTILIZATION AND PROGRESS TOWARD ELIMINATING USE OF HIGHLY ENRICHED URANIUM S. JAMES ADELSTEIN, Chair, Harvard Medical School, Boston, Massachusetts THOMAS J. RUTH, Vice-Chair, TRIUMF, Vancouver, British Columbia, Canada (emeritus) LIN-WEN HU, Massachusetts Institute of Technology, Cambridge, Massachusetts JOSEPH C. HUNG, Mayo Clinic, Rochester, Minnesota ROBERT T. JUBIN, Oak Ridge National Laboratory, Oak Ridge, Tennessee EMMETT B. KEELER, Pardee RAND Graduate School, Santa Monica, California GERALD L. KULCINSKI, University of Wisconsin–Madison JASON S. LEWIS, Memorial Sloan Kettering Cancer Center, New York, New York KATHRYN A. MORTON, University of Utah, Salt Lake City EUGENE J. PETERSON, Los Alamos National Laboratory, Los Alamos, New Mexico TOR RAUBENHEIMER, SLAC National Accelerator Laboratory, Menlo Park, California HENRY D. ROYAL, Washington University School of Medicine, St. Louis, Missouri FELICIA L. TAW, Los Alamos National Laboratory, Los Alamos, New Mexico Staff KEVIN D. CROWLEY, Study Director OURANIA KOSTI, Senior Program Officer TONI GREENLEAF, Administrative and Financial Associate DARLENE GROS, Senior Program Assistant v Copyright © National Academy of Sciences. All rights reserved. Molybdenum-99 for Medical Imaging Copyright © National Academy of Sciences. All rights reserved. Molybdenum-99 for Medical Imaging NUCLEAR AND RADIATION STUDIES BOARD ROBERT C. DYNES, Chair, University of California, San Diego JAMES A. BRINK, Vice Chair, Massachusetts General Hospital, Boston GEORGE E. APOSTOLAKIS, Massachusetts Institute of Technology (emeritus), Cambridge DAVID J. BRENNER, Columbia University, New York MARGARET S. Y. CHU, M.S. Chu & Associates, LLC, New York, New York TISSA H. ILLANGASEKARE, Colorado School of Mines, Golden CAROL M. JANTZEN, Savannah River National Laboratory, Aiken, South Carolina MARTHA S. LINET, National Institutes of Health, Bethesda, Maryland NANCY JO NICHOLAS, Los Alamos National Laboratory, Los Alamos, New Mexico HENRY D. ROYAL, Washington University School of Medicine, St. Louis, Missouri DANIEL O. STRAM, University of Southern California, Los Angeles WILLIAM H. TOBEY, Belfer Center for Science and International Affairs, Cambridge, Massachusetts SERGEY V. YUDINTSEV, Russian Academy of Sciences, Moscow Staff KEVIN D. CROWLEY, Director JENNIFER HEIMBERG, Senior Program Officer OURANIA KOSTI, Senior Program Officer TONI GREENLEAF, Administrative and Financial Associate LAURA D. LLANOS, Administrative and Financial Associate DARLENE GROS, Senior Program Assistant vii Copyright © National Academy of Sciences. All rights reserved. Molybdenum-99 for Medical Imaging Copyright © National Academy of Sciences. All rights reserved. Molybdenum-99 for Medical Imaging Acknowledgments he successful completion of this study would not have been possible Twithout the cooperation and assistance of many organizations and individuals. The committee would especially like to acknowledge and thank the following organizations and individuals for their support: Department of Energy’s National Nuclear Security Administration (NNSA), which sponsored the study and provided information on the agency’s activi- ties to establish domestic production and support international produc- tion of molybdenum-99 for medical use without highly enriched uranium. The committee would especially like to thank Jeffrey Chamberlin, Rilla Hamilton, Peter Karcz, Randy Howell, Thomas Hanlon, Tim Evans, and Crystal Trujillo. Rilla Hamilton served ably as the agency’s liaison to the committee and was effective in coordinating NNSA’s response to the com- mittee’s many requests for information. Department of Energy’s Office of Environmental Management: Theresa Kliczewski and Hitesh Nigam for providing information on the uranium and lease take-back program. Other federal agencies involved in establishing molybdenum-99 produc- tion that provided information on their regulatory processes and activities. The committee thanks Eric Duffy, Food and Drug Administration; Daniel Duvall, Centers for Medicare & Medicaid Services; and Steven Lynch, U.S. Nuclear Regulatory Commission. ix Copyright © National Academy of Sciences. All rights reserved. Molybdenum-99 for Medical Imaging x ACKNOWLEDGMENTS U.S. National Laboratories: Argonne National Laboratory (ANL), Los Alamos National Laboratory, Oak Ridge National Laboratory, Savannah River National Laboratory, and Y-12 National Security Complex, which provided information on the NNSA-supported research and development for establishing domestic production of molybdenum-99 for medical use without highly enriched uranium (see