PROSPECTS FOR THE PRODUCTION OF THERAPEUTIC RADIOISOTOPES BASED ON INSTALLED CAPACITY IN ARGENTINA AND BRAZIL

Abstract

Therapeutic radioisotopes were first used in clinical practice in 1941 to treat thyroid cancer, using a mixture of ¹³¹I/¹³³I produced in a cyclotron. Nowadays, high-purity ¹³¹I is still used to treat thyroid disease, but it is produced in nuclear reactors. From the 1980s to the 2010s, new radioisotopes were introduced for cancer treatment, including beta (β) emitter ⁹⁰Y, ¹⁵³Sm, and ¹⁶⁶Ho. By the end of 2010, ¹⁷⁷Lu emerged as a promising radioisotope for theranostic applications, and by 2020, ¹⁶¹Tb was identified as a promising new radioisotope due to its simultaneous β and Auger-electron emission. Also, the alpha emitters ²¹¹At, ²²⁵Ac, ²¹²Pb, and ²¹³Bi have proven effective in cancer treatment.

Requirements for radioisotopes production

The production of these radioisotopes depends on specific nuclear reactions requiring either high-energy charged particles or high neutron fluxes. For ²²⁵Ac, several methods were tested, one of the oldest is ²³²Th(p,x)²²⁵Ac, >100 MeV. However, this route is controversial because it co-produces ²²⁷Ac, a long half-life (21.7 y) alpha emitter, that makes impossible it uses in humans; alternatively ²²⁶Ra(p,2n)²²⁵Ac ≥ 30 MeV; other possibility is ²²⁶Ra(g,n)²²⁵Ra (β)²²⁵Ac has been in use to produce ²²⁵Ac with the higher radionuclide purity, ²⁰⁹Bi(α,2n)²¹¹At, but with alpha particles not higher than 29-28 MeV to avoid production to ²¹¹Po, ¹⁵¹Eu(³He,5n)¹⁴⁹Tb 40-70 MeV. Beyond the production of standard beta-emitting radioisotopes, current research focuses on the ¹⁶⁰Gd(n,γ)¹⁶¹Gd(β)¹⁶¹Tb (thermal neutron flux, in the range of 10¹³ to 10¹⁴ n.cm^-2.s^-1).

Reactor and cyclotron production capability in Argentina and Brazil

Argentina and Brazil have installed 10 research reactors, but only three of them, RA-3 (10 MW, neutron 1-1.4 × 10¹⁴) and RA-10 (30 MW, 1.4-2.5 × 10¹⁴ (expected to be critical in 2027), by CNEA, in Argentina, and the IEA-R1 (4.5 MW, 1 × 10¹⁴) in Brazil have the capacity to produce of therapeutic radioisotopes in commercial scale. From these, Ra-3 is producing ⁹⁹Mo, ⁵¹Cr, ¹³¹I and ¹⁷⁷Lu, and ¹⁶¹Tb under R&D production. Currently, the IEA-R1 is not producing radioisotopes, but it is planned to return to the production of ¹³¹I and start the ¹⁷⁷Lu production in 2026. Furthermore, Brazil has begun construction of the Brazilian Multipurpose Reactor (RMB), which will operate at 30 MW and is scheduled to begin operations in 2032. There are 26 cyclotrons installed in the region, but a limited number can operate above 20 MeV, restricting the production of advanced therapeutic radionuclides. Argentina has the CP-42 (42 MeV), which is in maintenance and returning at the end of 2026, and a new center is planned to operate a 30 MeV Cyclotron in 2029, focusing on ²²⁵Ac production for industrial applications. In Brazil, the IPEN is investing in cyclotron-based production of ²²⁵Ac via the ²²⁵Ra (p,2n)²²⁵Ac using its 30 MeV cyclotron. In parallel, IPEN has established partnerships with multinational companies to process and purify ²²⁶Ra, supporting a sustainable and scalable ²²⁵Ac supply chain.

Conclusion: The production and distribution of emerging therapeutic radioisotopes require substantial and specialized human resources, which constrain access in the region. The commissioning of new reactors, particularly RA-10 and the RMB, is expected to significantly enhance regional capabilities, while cyclotron-based production remains largely restricted to conventional medical radionuclides.