Research and Development for Cyclotron Production of 225Ac from 226Ra—The Challenges in a Country Lacking Natural Resources for Medical Applications

Abstract

The high therapeutic effect of targeted radioisotope/radionuclide therapy (TRT) using α-emitters, especially 225Ac, is attracting attention worldwide. However, the only 225Ac production method that has been put into practical use is extraction from a 229Th generator derived from the nuclear fuel 233U, and it is unlikely that this method alone is able to meet future global medical demand. Development towards new 225Ac production methods is in progress. These new 225Ac production methods require the irradiation of 232Th or 226Ra using an accelerator or a nuclear reactor. Global competition has already begun in the race to secure a reliable supply of 232Th and 226Ra, as well as 229Th for the conventional production method. Japan is a “resource-poor country” that depends on foreign countries for most of its needs. As such, it is difficult for Japan to secure raw materials such as 232Th and 226Ra for medical application. In this paper, we look back on our research at the National Institutes for Quantum Science and Technology (QST) in the fields of 225Ac production and 225Ac-labeled pharmaceutical development. We present the history and details of our research from 2011, as well as the development of a collaboration between QST and Nihon Medi-Physics that focuses on research into 225Ac production via 226Ra(p,2n)225Ac reaction using an accelerator. Furthermore, we review the valuable discussion at the 2018 Joint IAEA-JRC Workshop—“Supply of Actinium-225”, an international conference that we participated in. Overall, the statuses of external 225Ac supply, domestic production, and distribution are discussed, as are the latest developments in 225Ac production methods, 225Ac pharmaceuticals, and future prospects for the domestic production of 225Ac in Japan, a country lacking natural resources for medical applications.

Alpha-Emitting Radionuclides: Current Status and Future Perspectives

“…There are various nuclear reactions either producing 225 Ac directly or providing the parent radionuclide thorium-232, thorium-229 or radium-225, alternatively. These include but are not limited to: 226 Ra(γ,,n) 225 Ra → 225 Ac (accelerator, electrons); 226 Ra(p,2n) 225 Ac, 226 Ra(α,n) 229 Th, 232 Th(p,x) 229 Th, 226 Ra(p,pn) 225 Ra, (accelerator, low-energy particles); 232 Th(p,x) 225 Ac, 232 Th(p,x) 225 Ra → 225 Ac (accelerator, high-energy particles); and 226 Ra(3n, γ) 229 Ra → 229 Ac → 229 Th (reactor, thermal neutrons) [ 7 , 8 , 9 ].…”

Targeted Alpha Therapy: All We Need to Know about 225Ac’s Physical Characteristics and Production as a Potential Theranostic Radionuclide

“…Furthermore, during the time needed for target cooling and reprocessing, their activity will continue to decrease to low levels. Handling targets that contain milligram amounts of radioactive 226 Ra (T 1/2 = 1600 y) and controlling its highly radiotoxic gaseous decay product 222 Rn (T 1/2 = 3.8 d) [5,14,98,100] pose significant challenges in the production, processing, and control procedures [5,78]. In addition, due to the limited availability of the target material, it is necessary to consider its recycling process [20].…”

“…Currently, facilities in North and South America, Europe, and Asia are researching how to utilise this production strategy. For instance, work on the investigation and development of 225 Ac generation using 226 Ra (stored as radioactive waste) has started at the National Institutes for Quantum Science and Technology (QST), Chiba, Japan [100]. These amounts of 226 Ra have previously been used as a sealed source for brachytherapy.…”

“…These amounts of 226 Ra have previously been used as a sealed source for brachytherapy. Even in this resource-constrained country, some 226 Ra was accessible as a target for proton irradiation thanks to the national waste management program [100].…”

Production of 225Ac for medical application from 232Th-metallic targets in Nb-shells irradiated with middle-energy protons

“…There are about 15 projects worldwide for the production of 225 Ac or 229 Th from 226 Ra-containing targets. 17 Different methods are reported, in particular irradiation of radiumcontaining targets with protons, [18][19][20] deuterons, 21 gamma quanta 22 or neutrons 23,24 followed by the recovery of 225 Ac or 229 Th from the irradiated targets by ion exchange and other chemical methods. Generally, radium salts, e.g., carbonate, nitrate or chloride are used as target materials.…”