MEDICAL ISOTOPE PRODUCTION

Abstract

Nearly 95 percent of the world demand for molybdenum-99 (Mo-99)—perhaps the world's most important medical isotope—is met by just four manufacturers, all of whom use highly enriched uranium (HEU) targets in their isotope production programs. Research and development on the use of low-enriched uranium targets and gel generators to produce Mo-99 began in the 1980s; some success has been achieved, but Mo-99 is still mainly produced by irradiating HEU targets in a reactor. Fission-produced Mo-99 has a high specific activity, but activation methods provide low specific activity Mo-99, which is unsuitable for the generators routinely used in most of the world's medical centers. This article evaluates the use of enriched Mo-98 to produce Mo-99 by activation methods; the use of medium specific activity Mo-99 for the preparation of alumina-based generators is also discussed. This article concludes that if support is provided for the production of enriched Mo-98, it may replace to a significant extent the use of HEU and LEU for the production of Mo-99.

Keywords:

• Medical isotopes
• molybdenum
• technetium
• low-enriched uranium
• highly enriched uranium
• RERTR

Acknowledgements

The author would like to thank all the individuals involved in the production, supply, and use of Mo-99 and Tc-99m, particularly the participants in the IAEA's CRP, for their efforts to ensure globally available Mo-99 supplies. All opinions and any errors are the responsibility of the author alone.

Notes

1. Technetium-99m radiopharmaceuticals are used in several diagnostic procedures, for example, for imaging neuroendocrine tumors. Owing to its multiple oxidation states, Tc-99m has a versatile chemistry, making it possible to produce a variety of complexes with specific desired characteristics—a major advantage of Tc-99m for radiopharmaceutical development. There are hundreds of Tc-99m complexes useful for diagnostic procedures, more than thirty of which are used in clinical studies. Tc-99m radiopharmaceuticals are generally formulated from kits prepared at authorized manufacturing facilities.

2. For more on the various risks associated with medical isotope production, see Cristina Hansell, “Nuclear Medicine's Double Hazard: Imperiled Treatment and the Risk of Terrorism,” Nonproliferation Review 15 (July 2008), pp. 185–208.

3. HEU is uranium in which the percentage of the fissionable isotope U-235 is increased to 20 percent or more beyond the content of 0.7205 percent in naturally occurring uranium.

4. IAEA, “Fission Molybdenum-99 for Medical Use,” IAEA-TECDOC-515, International Atomic Energy Agency, Vienna, 1989; IAEA, “Production Technologies for Molybdenum-99 and Technetium-99m,” IAEA-TECDOC-1065, 1999.

5. IAEA, “Alternative Technologies for Tc-99m Generators: Final Report of a Coordinated Research Programme 1990–1994,” IAEA-TECDOC-852, 1995.

6. P. Saraswathy et al., “Tc-99m Generators for Clinical Use Based on Zirconium Molybdate Gel and (n, gamma) Produced Mo-99: Indian Experience in the Development and Deployment of Indigenous Technology and Processing Facilities,” paper presented at the 2007 International Reduced Enrichment for Research and Test Reactors Meeting, Prague, September 23–27, 2007. The general procedure for preparation of zirconium molybdate (Mo-99) involves careful mixing of equimole quantities of sodium molybdate (Mo-99) solution and zirconyl chloride solution at 60 degrees Celsius, digestion of the precipitate, rapid filtration, drying under controlled conditions, fragmentation of dried cake, re-drying, and dispensing the free-flowing of zirconium molybdate (Mo-99) granules into glass columns.

7. IAEA, “Radioisotope Production and Quality Control,” Technical Report Series 128, 1971.

8. U.T. Ashrapov, S. Khujaev, “The Stationary Generator of the Technetium-99m,” Institute of Nuclear Physics, Academy of Sciences of the Republic of Uzbekistan, Proceedings of the Second Eurasian Conference, Nuclear Science and Its Application, vol. I (2002), pp. 499–503.

9. S. Khujaev, N.A. Mirzaeva, U.T. Ashrapov, L.B. Nushtaeva, M. Berdieva, “Regeneration of Enriched Mo-98 from Waste Tc-99m Generators,” Institute of Nuclear Physics, Academy of Sciences of the Republic of Uzbekistan, Proceedings of the Second Eurasian Conference, Nuclear Science and Its Application, vol. I (2002), pp. 455–58.

10. Reduced Enrichment for Research and Test Reactors, Nuclear Engineering Division, Argonne National Laboratory, <www.rertr.anl.gov/>; IAEA, Research Reactor Group, Eurasia Research Reactor Coalitions, <www.iaea.org/OurWork/ST/NE/NEFW/rrg_EARRC.html>.

11. I. Goldman, N. Ramamoorthy, P. Adelfang, “Fostering New Sources of Mo-99 for International Nuclear Medicine Needs,” IAEA paper on the CRP at the 2007 RERTR conference, <www.iaea.org/OurWork/ST/NE/NEFW/rrg_Mo99.html>.

12. A.I. Ryabchikov, V.S. Skuridin, E.S. Nesterov, E.V. Chibisov, and V.M. Golovkov, “Obtaining Molybdenum-99 in the IRT-T Research Reactor Using Resonance Neutrons,” Nuclear Instruments and Methods in Physics Research, B 213 (2004), p. 364.

13. S. Mirzadeh, C.W. Alexander, and F.F. Knapp Jr., “The Advanced Neutron Source (ANS)—A Proposed National Resource for Medical Radioisotope Production,” Journal of Nuclear Medicine 35 (1994), p. 245.

14. Ahmad Mushtaq, “Desorption of Mo-99 from Spent Mo-99/Tc-99m Generator,” Journal of Radioanalytical and Nuclear Chemistry Letters 199 (1995), p. 89; Ahmad Mushtaq, “Recovery of Enriched W-186 from Spent W-188/Re-188 Generator,” Applied Radiation and Isotope 47 (1996), p. 727.

15. In order to render the retrieval-recovery logistics of enriched Mo-98 more amenable for routine practice, the promotion of central radiopharmacies for housing and operating Tc-99m generators would be helpful. This approach would also help in greater effective use of the generator capacity, and of all Mo-99 produced.

16. The price of enriched Mo-98 was quoted in December 2008 by an agent at Trace Sciences Internationals Inc., Wilmington, DE.