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  • Perspective
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Future of 99Mo reactor-independent supply

Nature Reviews Physics (2024)Cite this article

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Abstract

Molybdenum-99 is essential for nuclear medicine, being the parent radionuclide of 99mTc, which is commonly used in single-photon-emission computed tomography scans. Worldwide, the supply of 99Mo has faced considerable disruption twice in recent years: in 2009 triggered by the unexpected simultaneous shutdown of two nuclear research reactors, and in 2020 because of disruption to shipments of 99Mo as a consequence of severe restrictions on flights. This Perspective therefore examines alternative means of 99Mo production, via cyclotrons, electron linear accelerators and fusion neutron sources. The research and development of methods for 99Mo that can be synergic and complementary to reactors in the short-to-medium term and alternative to them in the long term is strategic for addressing potential global events that might produce reduced access to healthcare procedures relying on diagnostic as well as therapeutic radionuclides.

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Fig. 1: Main physical characteristics for 99Mo production by means of fission nuclear reactors.
Fig. 2: Weekly expected available capacity for 99Mo production for different fission reactors worldwide.
Fig. 3: Cross-sections of 99Mo production relevant for the three alternative approaches discussed in this Perspective.
Fig. 4: Cross-section of the 100Mo(e,e′n)99Mo reaction as used by the FLUKA-CERN code42,43.
Fig. 5: Estimated fraction of the Italian weekly demand for 99Mo/99mTc covered by different production methods.

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References

  1. Morillon, C., Bé, M. M., Chechev, V. & Egorov, A. Tc-99m. Table of Radionuclides Vol. 1 www.lnhb.fr/nuclides/Tc-99m_tables.pdf (2004).

  2. Eckelman, W. C. Unparalleled contribution of technetium-99m to medicine over 5 decades. JACC Cardiovasc. Imaging 2, 364 (2009).

    Article  Google Scholar 

  3. Israel, O. et al. Eur. J. Nucl. Med. Mol. Imaging 46, 1990 (2019).

    Article  Google Scholar 

  4. Morillon, C., Bé, M. M., Chechev, V. & Egorov, A. Mo-99. Table of Radionuclides Vol. 1 www.lnhb.fr/nuclides/Mo-99_tables.pdf (2004).

  5. Nuclear Energy Agency. The Supply of Medical Radioisotopes: An Assessment of Long-Term Global Demand for Technetium-99m (OECD, 2020).

  6. Nuclear Energy Agency. The Security of Supply of Medical Radioisotopes Demand and Capacity Projections for 99Mo/99mTc for the 2023–2027 Period (OECD, 2023).

  7. Dittrich, S. History and actual state of non-HEU fission-based Mo-99 production with low-performance research reactors. Sci. Technol. Nucl. Install. 2013, 1–9 (2013).

    Article  Google Scholar 

  8. Nuclear Energy Agency. The Supply of Medical Radioisotopes: Review of Potential Molybdenum-99/Technetium-99m Production Technologies (OECD, 2020).

  9. Le, V. S. 99mTc generator development: up-to-date 99mTc recovery technologies for increasing the effectiveness of 99Mo utilisation. Sci. Technol. Nucl. Install. 2014, 345252 (2014).

    Article  Google Scholar 

  10. Gould, P. Medical isotope shortage reaches crisis level; robust solutions sought urgently to shore up fragile supply chain. Nature 460, 312–313 (2009).

    Article  Google Scholar 

  11. Van Noorden, R. Radioisotopes: the medical testing crisis. Nature 504, 202–204 (2013).

    Article  ADS  Google Scholar 

  12. IAEA. Non HEU Production Technologies for Molybdenum-99 and Technetium-99m. Nuclear Energy Series No. NF-T-5.4 (IAEA, 2013).

  13. International Civil Aviation Organization. Effects of Novel Coronavirus (COVID‐19) on Civil Aviation: Economic Impact Analysis (ICAO, 2021).

  14. Mo-99 supply put at risk by COVID-19 pandemic. Nuclear Newswire http://www.ans.org/news/article-67/mo99-supply-put-at-risk-by-covid19-pandemic/ (7 April 2020).

  15. Gagnon, K. et al. Cyclotron produced Tc-99m on a TR24 high current target station. J. Nucl. Med. 55, 1195 (2014).

    Google Scholar 

  16. Martini, P. et al. In-house cyclotron production of high-purity Tc-99m and Tc-99m radiopharmaceuticals. Appl. Radiat. Isot. 139, 325–331 (2018).

    Article  Google Scholar 

  17. Tsechanski, A., Bielajew, A. F., Archambault, J. P. & Mainegra-Hing, E. Electron accelerator-based production of molybdenum-99: bremsstrahlung and photoneutron generation from molybdenum vs. tungsten. Nucl. Instrum. B 366, 124–139 (2016).

    Article  ADS  Google Scholar 

  18. Bennet, R. G., Christian, J. D. & Petti, D. A. A system of 99mTc production based on distributed electron accelerators and thermal separation. Nucl. Technol. 126, 102–121 (1999).

    Article  ADS  Google Scholar 

  19. Nagai, Y. et al. Generation of radioisotopes with accelerator neutrons by deuterons. J. Phys. Soc. Jpn 82, 064201 (2013).

    Article  ADS  Google Scholar 

  20. Schmor, P. Review of cyclotrons for the production of radioactive isotopes for medical and industrial applications. Rev. Accel. Sci. Technol. 4, 103–116 (2011).

    Article  Google Scholar 

  21. Chao, A. W. & Chou, W. Rev. Accel. Sci. Technol. 10, 105 (2019).

    Article  Google Scholar 

  22. IAEA. Cyclotron Produced Radionuclides: Principles and Practice. IAEA Technical Reports Series No. 465 (IAEA, 2009).

  23. Gagnon, K. et al. Cyclotron production of 99mTc: experimental measurement of the 100Mo(p,x)99Mo, 99mTc and 99gTc excitation functions from 8 to 18 MeV. Nucl. Med. Biol. 38, 907–916 (2011).

    Article  Google Scholar 

  24. Buckley, K. Cyclotron production of Tc-99m. In Proc. Cyclotrons 2013 FR2PB02, 482–486 (2013).

  25. Berman, B. L. & Fultz, S. C. Measurements of the giant dipole resonance with monoenergetic photons. Rev. Mod. Phys. 47, 713–761 (1975).

    Article  ADS  Google Scholar 

  26. Danos, M., Ishkhanov, B. S., Eramjan, R. A. & Yudin, N. P. Giant dipole resonance and the evolution of concepts of nuclear dynamics. Usp. Fiz. Nauk 165, 1345–1355 (1995).

    Article  Google Scholar 

  27. Spicer, B. M. in Advances in Nuclear Physics (eds Baranger, M. & Vogt, E.) 1–78 (Springer, 1969).

  28. Fong, A., Meyer, T. I. & Zala, K. (eds) Making Medical Isotopes: Report of the Task Force on Alternatives for Medical-Isotope Production (TRIUMF, 2008).

  29. Balashov, V. V., Grishanova, S. I., Kabachnik, N. M. & Kulikov, V. M. Unified description of inelastic and quasielastic electron scattering from nuclei. Phys. Lett. B 36, 325–327 (1971).

    Article  ADS  Google Scholar 

  30. Friedman, J. I. & Kendall, H. W. Deep inelastic electron scattering. Ann. Rev. Nucl. Sci. 22, 203–254 (1972).

    Article  ADS  Google Scholar 

  31. Boffi, S., Giusti, C., Pacati, F. D. & Radici, M. Electromagnetic Response of Atomic Nuclei (Clarendon, 1996).

  32. Tsechanski, A., Fedorchenko, D. & Starovoitova, V. On the contribution of the electronuclear reaction to the photonuclear production of Mo-99 and other radioisotopes. Rad. Phys. Chem. 177, 109108 (2020).

  33. Pietropaolo, A. et al. The Frascati neutron generator: a multipurpose facility for physics and engineering. J. Phys. Conf. Ser. 1021, 012004 (2018).

  34. Martone, M., Angelone, M. & Pillon, M. The 14 MeV Frascati neutron generator. J. Nucl. Mat. 212–215, 1661–1664 (1994).

    Article  ADS  Google Scholar 

  35. Capogni, M., Pietropaolo, M. & Quintieri, L. 99mTc Production via 100Mo(n,2n)99Mo Using 14 MeV Neutrons from a D–T Neutron Source: Discussion for a Scientific Case. Report No. ENEA-RT-2016-32 (ENEA, 2016).

  36. Capogni, M. et al. 14 MeV neutrons for 99Mo/99mTc production: experiments. Simul. Perspect. Molecules 23, 1872 (2018).

    Google Scholar 

  37. Pietropaolo, A. et al. SORGENTINA-RF project: fusion neutrons for 99Mo medical radioisotope. Eur. Phys. J. 136, 1140 (2021).

    Google Scholar 

  38. Pietropaolo, A., Capogni, M. & Quintieri, L. Secure molybdenum isotope supplies for diagnostics. Nature 603, 393 (2022).

    Article  ADS  Google Scholar 

  39. SHINE medical isotope production facility, Janesville, Wisconsin. www.pharmaceutical-technology.com/projects/shine-medical-isotope-production-facility/ (9 March 2018).

  40. Cervenák, J. & Lebeda, O. Experimental cross-sections for proton-induced nuclear reactions on natMo. Nucl. Instrum. Methods Phys. Res. B 380, 32–49 (2016).

    Article  ADS  Google Scholar 

  41. Handbook on Photonuclear Data for Applications: Cross-Sections and Spectra 186 (IAEA, 2000).

  42. Ahdida, C. et al. New capabilities of the FLUKA multi-purpose code. Front. Phys. 9, 788253 (2022).

  43. Battistoni, G. et al. Overview of the FLUKA code. Ann. Nucl. Energy 82, 10–18 (2015).

    Article  Google Scholar 

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Acknowledgements

The authors thank A. Duatti for discussions.

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Authors and Affiliations

  1. ENEA, Department of Fusion and Technologies for Nuclear Safety and Security, Rome, Italy

    Antonino Pietropaolo & Marco Capogni

  2. ENEA, Italian National Institute of Ionizing Radiation Metrology, Rome, Italy

    Marco Capogni

  3. Science and Technology Facilities Council, ISIS Neutron & Muon source, Harwell, UK

    Lina Quintieri

Authors
  1. Antonino Pietropaolo
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  2. Marco Capogni
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  3. Lina Quintieri
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All authors contributed to conceptualization, writing, revisions and analysis presented in the Perspective.

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Correspondence to Antonino Pietropaolo.

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Related links

DAFNE: https://w3.lnf.infn.it/accelerators/dafne/

Experimental Nuclear Reaction Data (EXFOR): https://www-nds.iaea.org/exfor/

FACET-II: https://facet-ii.slac.stanford.edu/

FLUKA-CERN: https://fluka.cern

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Pietropaolo, A., Capogni, M. & Quintieri, L. Future of 99Mo reactor-independent supply. Nat Rev Phys (2024). https://doi.org/10.1038/s42254-024-00716-1

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