# Isotopes for the Nation’s Future

Donald F. Geesaman and Ani Aprahamian

Introduction

In the October 2009 edition of Physics & Society, Tom Ruth described some of the history of how the current medical isotope crisis came to be. In addition to medical applications, stable and radioactive isotopes are essential tools in a wide variety of technological, engineering, environmental, and materials-sciences enterprises. The value of US isotope shipments is approximately $3 billion annually [1]. Recent news headlines have focused on the impact of isotope shortages on medicine, homeland security, and basic science. These include the shortage of molybdenum-99 (Mo-99), the most commonly used medical isotope, and helium-3 (He-3), an isotope critical for both national security and low temperature research [New York Times, 23 July and 22 November 2009]. On November 18, 2009, the House of Representatives overwhelmingly passed HR 3267, the Medical Isotope Bill, encouraging the production of Mo-99 in the United States. None is being produced in the US at this writing. This article reviews the current and proposed federal involvement in isotope production. DOE Isotope Development and Production for Research and Applications Program Federal involvement with isotope production began with the Atoms for Peace initiative of President Eisenhower. While today private producers are the main suppliers in the isotope markets, they have benefited from and continue to be significantly affected by DOE involvement. In 2009, management of the isotope program within DOE was transferred from the Office of Nuclear Energy to the Office of Nuclear Physics of the Office of Science, at which time the program was renamed the Isotope Development and Production for Research and Applications Program (IDPRA, or simply Isotope Program). Today, the DOE Isotope Program focuses on isotopes where it has unique capabilities, research isotopes where the demand is limited and often sporadic, and research and development of isotope production techniques. The mission of the IDPRA is threefold: • Produce and sell radioactive and stable isotopes that are in short supply, associated byproducts, surplus materials and related isotope services. • Maintain the infrastructure required to supply products and related services. • Conduct R&D on new and improved isotope production and processing techniques. The IDPRA is a relatively small federal program funded by appropriations (FY08$14.8M) and sales (FY08 $17.1M). It has stewardship responsibilities for two facilities whose primary missions are isotope production. The Brookhaven Linac Isotope Producer, a 200 MeV proton linear accelerator and associated radiological work areas (hot-cells) at Brookhaven National Laboratory, was built in 1972 to utilize beams from what is now part of the Relativistic Heavy Ion Collider. The Isotope Production Facility and associated hot-cells at Los Alamos National Laboratory were completed in 2004 and utilize beams from the Los Alamos Neutron Science Center LANSCE accelerator complex. Oak Ridge National Laboratory hosts the Isotope Business Office, which coordinates all isotope sales, including those made elsewhere and the stockpile of stable isotopes that were previously produced at the now-mothballed Calutrons, the National Isotope Data Center, and materials processing facilities and hot-cells. The Isotope Program also supports a suite of laboratory and university facilities for isotope production, such as the ORNL High Flux Isotope Reactor, which is stewarded by Basic Energy Sciences. These additional production facilities are funded for primary missions apart from isotope production. This allows significant cost efficiencies in the isotope production enterprise while simultaneously presenting challenges in scheduling needed isotope production around other constraints which are not under the control of IDPRA operations. IDPRA also acts as a sales broker for He-3 harvested at Savannah River during the maintenance of nuclear weapons. Other facilities and resources within the DOE complex have been applied to isotope production in the past and will likely continue to be utilized in the future when specialized capabilities are needed. These include the Advanced Test Reactor at Idaho National Laboratory and hot cells and various stockpiles of irradiated targets stored at several national laboratories. IDPRA does not have responsibility for certain critical isotopes, including weapons materials such as tritium, enriched uranium, and plutonium. For example, the responsibility related to the production of Mo-99 has been assigned to DOE/NNSA. This is mainly because the most common production method of Mo-99 in reactors uses highly enriched U-235, and is thus a proliferation concern. Legislation in the 1990’s substantially modified the operation of the Isotope Program, and imposed the requirement for full cost recovery for isotope sales. Since 2003, research isotopes have been priced based on production cost while commercial isotopes continued to be sold at full cost. Over the past two decades, these requirements have lead to a sizable down-sizing of the isotope program due to foreign competition and increased reliance on foreign suppliers. For example, the Y-12/ORNL Calutron stable-isotope separation capability was shut down in 1998 leaving no significant US production capability for a large number of stable isotopes. Reduced missions in aspects of national security have also led to reliance on foreign supplies. Numerous expert panels and advisory committee reports over the past decade have pointed out the risk of relying solely on limited foreign suppliers [2,3]. It is not an exaggeration to say that research and clinical studies of essential mineral nutrient metabolism in humans, as well as a broad array of environmental and ecological studies, would come to a complete halt if the supply of these isotopes were curtailed. Challenges to the Isotope Program and Proposals for Future Priorities There are a number of challenges facing the isotope program. The need for research isotopes comes from many federal agencies. Promising research opportunities vary from year to year. To be responsive, the program must maintain broad and expensive capabilities, which require highly trained teams of experts that cannot be easily replaced. These capabilities often have significant environment, health and safety implications. Once in operation, the facilities may not be continuously in use due to fluctuating demand. In taking advantage of the capital investments of other parts of the DOE program, the isotope production utilization is subject to the changing mission priorities of those programs, leading to operating schedules or even facility closure decisions beyond the isotope program's control. Many radioisotopes must be used within hours or days of production and treatment regimes require stable long-term availability, but the program currently has no accelerator facility available for the continuous production of isotopes [3]. If a new medical application appears promising, large increases in production are required to support later-stage trials. If a commercial supplier enters the market, they may petition the government to withdraw from a competitive market. If an application fails to perform, the demand may collapse completely. Another aspect is volatility in the market place. For example, if a major customer withdraws from the market the cost for DOE to produce a given quantity of an isotope, and therefore the cost DOE is required to charge other users can increase dramatically on very short notice. At the same time, foreign suppliers, in many cases subsidized by their governments or capitalizing on previous government stocks, can often artificially determine the price that can be charged. This situation greatly increases the risk for a commercial entity to enter the market, placing a greater dependency on the federal program. When foreign governments subsidize research isotopes for their own researchers, U.S. researchers can be put at a significant disadvantage. Over the past year, the Department of Energy has made significant efforts to address some of the issues of the program. Funding in 2009 and 2010 was increased relative to 2008 levels and included funds for research and development and increased production of research isotopes. American Recovery and Reinvestment Act (ARRA) funds in the amount of$14.7M were allocated to enhance isotope production capabilities to better meet the needs of the nation for isotopes in short supply and to improve America's competitiveness by investing in isotope production research at universities and laboratories. A workshop was held in 2008 to bring together the varied stakeholders in the isotopes enterprise [4] to identify compelling opportunities with radioactive and stable isotopes and future isotope needs. Interagency working groups have been set up to improve coordination and planning, for example, by defining the future isotope needs of the National Institutes of Health and addressing the projected shortfall in the supply of He-3.

The Nuclear Science Advisory Committee (NSAC) is the advisory committee chartered to provide advice to the DOE Office of Nuclear Physics. In August 2008, in anticipation of the transfer of the Isotope Program to the Office of Nuclear Physics, NSAC was charged to identify the most compelling research opportunities with isotopes and to develop a long-range plan for the IDPRA program. NSAC formed a panel of experts, the NSAC Isotopes Subcommittee (NSACI), to carry out these tasks (The authors are co-chairs of this subcommittee). NSACI membership included physicians, pharmacists, research scientists, forensic experts and representatives of the isotope production industry. The full subcommittee membership, charges, and agendas for meetings can be found on the web [5]. Links to the charges and the two resulting reports, “Compelling Research Opportunities with Isotopes” and “Isotopes for the Nation’s Future: a long range plan” can be found there and at the NSAC web site [6]. The final report of the NSACI subcommittee presenting the long-range strategic plan was endorsed by NSAC on November 5, 2009, and transmitted to the DOE. Recommendations presented in the report are summarized below. Those in the first category are listed in order of priority. The second category addresses the issue of the dwindling population of skilled workers in areas related to isotope production and applications, a widely documented concern. Within the broad need, this recommendation is focused on the needs of the IDPRA program itself. Its relative priority is comparable to that for a sustained R&D program, with which it is closely linked. The third category addresses future needs. Due to the intense activity underway and active investigations of commercial alternatives led by the NNSA Global Threat Reduction Initiative, NSACI did not make specific recommendations on Mo-99, but did go on record that it was a major concern that must be addressed expeditiously.

(I) The Present Program

I.1: Maintain a continuous dialogue with all interested federal agencies and commercial isotope customers to forecast and match realistic isotope demand and achievable production capabilities.

I.2: Coordinate production capabilities and supporting research to facilitate networking among existing DOE, commercial, and academic facilities.

I.3: Support a sustained research program in the base budget to enhance the capabilities of the isotope program in the production and supply of isotopes generated from reactors, accelerators, and separators.

I.4: Devise processes for the isotope program to better communicate with users, researchers, customers, students, and the public and to seek advice from experts:

I.5: Encourage the use of isotopes for research through reliable availability at affordable prices.

I.6: Increase the robustness and agility of isotope transportation both nationally and internationally.

(II) Highly Trained Workforce for the Future

Invest in workforce development in a multipronged approach, reaching out to students, post-doctoral fellows, and faculty through professional training, curriculum development, and meeting/workshop participation.

(III) Major Investments in Production Capability

The present program, while highly flexible and responsive to the needs of the nation, lacks two major capacities that limit its ability to fulfill its mission. First, it presently has no working facilities for the separation of a broad range of stable and long-lived isotopes. Each year it is depleting its unique stockpile of isotopes to the point where some are no longer available. Second, many radioactive isotopes are short-lived and cannot be stockpiled. The current program relies on accelerators and reactors whose primary missions are not isotope production; thus, it is not in a position to provide continuous access to many of the isotopes.

III.1: Construct and operate an electromagnetic isotope separator facility for stable and long-lived radioactive isotopes.

It is recommended that such a facility include several separators for a raw feedstock throughput of about 300-600 milliAmpere (10-20 mg/hr multiplied by the atomic weight and isotopic abundance of the isotope). This capacity will allow yearly sales stocks to be replaced and provide some capability for additional production of high-priority isotopes.

III.2: Construct and operate a variable-energy, high-current, multi-particle accelerator and supporting facilities that have the primary mission of isotope production.

The most cost-effective option to ensure continuous access to many of the radioactive isotopes required is for the program to operate a dedicated accelerator facility. Given the uncertainties in future demand, this facility should be capable of producing the broadest range of interesting isotopes. Based on the research and medical opportunities considered by the subcommittee, a 30-40 MeV maximum energy, variable energy, high-current, multi-particle cyclotron seems to be the best choice on which to base such a facility.

The subcommittee gives somewhat higher overall priority to the electromagnetic isotope separator as there is no U.S. replacement. However, a solution in this area is not needed as urgently as the new accelerator capability. Therefore, in the subcommittee's optimum budget scenario that includes both, the construction of the new accelerator starts a year earlier.

The report discusses the implications of these recommendations in both an optimal budget scenario and a constant-level-of-effort-budget relative to the 2009 President's request of \$19.9M. Given the recent investments in the isotope program, constant-effort funding will allow the program to move forward from a more solid base for a few years. Once ARRA funding disappears, sustained constant-effort funding, while it does represent a needed increase from 2004-2008 levels, will place the infrastructure needs for research isotopes at risk in the long term and will not allow the program to address either of the two major missing capacities. The subcommittee does not consider this to be a wise course for the future. The subcommittee recommended an increased optimum budget that also includes new capital funds to realize the needed new capacities.

We hope the readers of Physics and Society will take the time to examine to the full reports of the NSACI and we welcome their input. The Office of Nuclear Physics has already begun to implement many of these recommendations within the existing IDPRA budget. The Subcommittee understands that all plans are a snapshot in time that must react to changing circumstances and looks forward to continuing to provide advice to DOE to help meet the nation's needs for isotopes.

References

[1] “Stable and Radioactive Isotopes”, United States International Trade Commission Industry and Trade Summary, Office of Industries Publication ITS-01, June 2009.

[2] M. J. Rivard et al., Appl. Rad. Isotopes 63, 157 (2005)

[3] “Advancing Nuclear Medicine Through Innovation”, National Research Council Committee on State of the Science of Nuclear Medicine (2007).

[4] “Workshop on the Nation's Needs for Isotopes: Present and Future”, J. Norenberg, P. Staples, R. Atcher, R. Tribble, J. Faught and L. Riedinger, http://www.sc.doe.gov/np/program/isotope.html (2008)

Ani Aprahamian and Donald Geesaman are the co-chairs of the NSAC Isotope Subcommittee. Prof. Aprahamian is a Professor of Physics at the University of Notre Dame. Dr. Geesaman is a Distinguished Argonne Fellow at Argonne National Laboratory. They would like to thank all the members of the NSAC Isotopes Subcommittee for their commitment and dedication to defining the future of the IDPRA program and also the many members of the community for their efforts to provide advise and information to the Subcommittee.

This contribution has not been peer refereed. It represents solely the view(s) of the author(s) and not necessarily the views of APS.