1

Background and Study Task

This study was mandated by the U.S. Congress in the American Medical Isotopes Production Act of 2012¹ (AMIPA) (see Appendix A):

The decay product³ of molybdenum-99 (Mo-99), technetium-99m⁴ (Tc-99m), and associated⁵ medical isotopes iodine-131 (I-131) and xenon-133 (Xe-133) are used worldwide for medical diagnostic imaging or therapy (see Sidebar 1.1). The United States consumes almost half of the world’s supply of Mo-99, but there has been no domestic (i.e., U.S.-based) production of this isotope since the late 1980s.⁶ The United States imports Mo-99 for domestic use from Australia, Canada, Europe, and South Africa.

Mo-99 and Tc-99m cannot be stockpiled for use because of their short

___________________

¹ Public Law 112-239.

² Now the National Academies of Sciences, Engineering, and Medicine, referred to as the “Academies” in this report.

³ Mo-99 decays to Tc-99m with a 66-hour half-life. See Chapter 2.

⁴ The letter “m” denotes that the isotope is metastable. See Chapter 2.

⁵ These isotopes are “associated” because they can be coproduced with Mo-99. See Chapter 2.

⁶ Cintichem, Inc., produced Mo-99 in Tuxedo, New York, until 1989.

half-lives.⁷ Consequently, they must be routinely produced and delivered to medical imaging centers. At present, almost all Mo-99 for medical use is produced by irradiating targets containing weapons-grade highly enriched uranium (HEU) (see Sidebar 1.2) in research and test reactors,⁸ some of which are over 50 years old (see Table 3.1 in Chapter 3). Unanticipated and extended shutdowns of some of these reactors have resulted in severe Mo-99 supply shortages in the United States and other countries. Some of these shortages have disrupted the delivery of medical care.

About 40-45 kilograms (kg) of weapons-grade HEU, mostly supplied

___________________

⁷ Half-life (denoted as t_½) is defined as the time required for half of the atoms of a given radioisotope to decay to another radioisotope.

⁸ Research and test reactors are used for scientific research, materials testing, and education/training. This report refers to these reactors as research reactors to be consistent with the usage in NASEM (2016). Sidebar 2.2 in Chapter 2 provides additional information about these reactors.

by the U.S. government,⁹ are used annually to produce these targets. Civilian use of HEU is a proliferation hazard because of the potential for its diversion by terrorists to make nuclear explosive devices (see Sidebar 1.2).

In enacting AMIPA, Congress was attempting to balance two national interests:

1. Ensure a reliable U.S. supply of Mo-99 and associated medical isotopes.

___________________

⁹ The U.S. government supplies HEU to Canada and Europe for production of medical isotopes. South Africa produces medical isotopes using indigenous HEU (and also using LEU that is currently supplied by Russia). See Chapter 5.

2. Eliminate the use of HEU in medical isotope production, especially in the targets used to produce medical isotopes.¹⁰

Congress recognized that these two interests were potentially in conflict; that is, elimination of HEU from medical isotope production without an alternate production method could affect the supply of Mo-99 to the United States. Congress provided additional provisions in AMIPA to promote the development of reliable domestic supplies of Mo-99 while also eliminating the use of HEU targets for its production. These include

• Technical and financial support to private-sector organizations for development of domestic production of Mo-99 without the use of HEU (see Chapter 5 of the present report for additional information);
• Leasing of low enriched uranium (LEU; see Sidebar 1.2) for domestic production of Mo-99 and take-back of radioactive waste from such production if alternate disposal pathways are not available (see Sidebar 4.1 in Chapter 4); and
• Phase-out of U.S. government exports of HEU for medical isotope production by 2020, with provision for extending this phase-out date if supplies of Mo-99 produced without HEU are not sufficient to meet U.S. needs (see Chapter 5).

The first and third provisions were suggested to Congress in the 2009 Academies report Medical Isotope Production Without Highly Enriched Uranium (NRC, 2009). The study that produced that report, which was mandated by the U.S. Congress in the Energy Policy Act of 2005, examined the technical and economic feasibility of producing medical isotopes without HEU. That study was motivated by a conflict between the objectives of the Energy Policy Act of 1992, which created increasing pressures to phase out HEU exports from the United States for medical isotope production, and the Energy Policy Act of 2005, which sought to increase the reliability of medical isotope supplies by permitting the export of HEU for medical isotope production, thus bypassing the requirements of the 1992 Act for HEU exports to Canada and Europe. That Academies’ study (NRC, 2009) concluded that production of medical isotopes without HEU was economically and technically feasible.

The Department of Energy’s National Nuclear Security Administra-

___________________

¹⁰ Some reactors used to irradiate targets for medical isotope production are fueled with HEU. The U.S. government has been supporting programs to eliminate the use of HEU in research reactor fuel since the late 1970s (see NASEM, 2016). Elimination of HEU in research reactor fuel is not addressed in the present report.

tion (DOE-NNSA) is the lead agency within the U.S. government for implementing AMIPA. The agency is well positioned to implement the non-proliferation provisions of AMIPA given its interest and expertise in non-proliferation. NNSA has teamed up with other parts of the U.S. government—for example, the Office of Science and Technology Policy within the White House, and the Centers for Medicare & Medicaid Services and the U.S. Food and Drug Administration within the Department of Health and Human Services—to promote domestic production of Mo-99 without HEU and to improve the reliability and sustainability of Mo-99/Tc-99m supplies. NNSA is also working with other national governments, primarily through the Organisation for Economic Co-operation and Development, to eliminate HEU from Mo-99 production and improve supply reliability and sustainability.

1.1 STATEMENT OF TASK FOR PRESENT STUDY

The Academies have carried out the AMIPA-mandated examination in two parallel studies:

• The present study examines the production and utilization of Mo-99 and associated medical isotopes, including the elimination of HEU in the reactor targets used for such production.
• A second Academies study examined the use of HEU research reactor fuel. This study was completed in early 2016 and published in the report titled Reducing the Use of Highly Enriched Uranium in Civilian Research Reactors (NASEM, 2016).

The complete statement of task for the present study is shown in Sidebar 1.3. Study charges 1, 2, 3, and the first part of study charge 5 explicitly address the AMIPA mandate. Study charge 4 and the last part of 5 (shown in italics in Sidebar 1.3) were added in consultation with the study sponsor, DOE-NNSA, to assist NNSA with its nuclear non-proliferation mission and to provide important additional information to the U.S. Congress and the medical isotope production and utilization communities.

Study charge 5 (Sidebar 1.3) calls for an assessment of progress made in eliminating HEU from reactor targets and medical isotope production facilities. It is important to recognize that medical isotopes can be produced in reactors fueled with HEU (see Chapter 3). The present study does not address the elimination of HEU from reactor fuel; that issue was addressed in NASEM (2016) as noted above.

1.2 STRATEGY TO ADDRESS THE STUDY TASK

The present study was carried out by a committee of 13 experts with collective expertise in accelerator design and operation, chemistry and radiopharmaceutical chemistry, medical economics, medical isotope production, nuclear engineering, nuclear medicine, nuclear pharmacy operations, and radioactive waste processing and management. In selecting the membership of this committee, the Academies sought to obtain a balance between members with experience in the production and isotope utilization in nuclear medicine, and members with relevant technical expertise but little-to-no direct experience with medical isotope production or utiliza-

tion. Two members of the committee, including its vice chair, also served on the committee that authored the Academies’ 2009 medical isotopes study (NRC, 2009). Biographical sketches of the committee members are provided in Appendix B.

The committee held six face-to-face meetings and additional teleconferences to gather the information it needed to complete this report. Information was gathered from the following organizations:

• The study sponsor (NNSA) and other federal agencies with responsibilities related to medical isotope production and utilization.
• Companies involved in the production, supply, and utilization of Mo-99/Tc-99m.
• Potential future U.S. suppliers of Mo-99.
• Potential future Canadian suppliers of Mo-99/Tc-99m.
• National laboratory experts who are providing technical support to current and potential future suppliers of Mo-99.
• International organizations with missions relevant to the reliability and sustainability of the medical isotope supply chain.
• Professional societies, including medical societies, as well as other nongovernmental organizations interested in the reliability and sustainability of medical isotope supply chains.

Subgroups of the committee also visited medical isotope production and supply facilities in Australia, Canada, Europe, Russia, and South Africa to learn about their operations and future plans. These information-gathering meetings and site visits are described in Appendix C.

The committee asked several organizations to perform accuracy checks on factual portions of this report during the Academies report review process.¹¹ These organizations included the study sponsor (NNSA) as well as current and potential future participants in the Mo-99/Tc-99m supply chain. The committee did not share the analytical portions of this report or the findings and recommendations with any outside persons or organizations.

1.3 REPORT ROAD MAP

This report is organized into seven chapters that address the statement of task (Sidebar 1.3) in its entirety:

• Chapter 1 (this chapter) provides background on the congressional mandate and describes the study task.

___________________

¹¹ These fact checks took place during July-August 2016.

• Chapter 2 provides technical information about Mo-99/Tc-99m production and utilization.
• Chapter 3 reviews the international production of Mo-99 for medical use since NRC (2009) was completed, and it examines future production prospects.
• Chapter 4 assesses progress toward establishing domestic production of Mo-99 for medical use.
• Chapter 5 reviews efforts to eliminate HEU from targets used for Mo-99 production.
• Chapter 6 reviews current and projected demand for Mo-99 for medical use.
• Chapter 7 describes the adequacy of current and projected Mo-99 supplies for medical use.

The appendixes provide the text from AMIPA (Appendix A), short biographies of the committee and staff (Appendix B), descriptions of the information-gathering activities for the study (Appendix C), a list of radiopharmaceuticals used to support the committee’s analysis of domestic Mo-99/Tc-99m demand in Chapter 6 (Appendix D), and a list of acronyms (Appendix E).