ИСТИНА

The development and trial of radiopharmaceuticals based on radionuclides with high linear energy transfer and short range in tissue (alpha-particles or Auger-electrons emitters) on the one hand, and highly specific delivery molecules on the other, is an essential step towards personalized medicine in the field of cancer treatment. Ac-225 (T1/2 = 9.9 days) and especially its decay product Bi-213 (46 min.) are proved to be promising for use in radiotherapy. More than 500 patients were treated with radiopharmaceuticals containing these radionuclides (up to 2018). A crucial problem of Ac-225 and Bi-213 wide application is their low availability. The generator method of Ac-225 production from Th-229 cannot satisfy the needs of even ongoing clinical trials. A prospective method of producing 225Ac (more than 1 Ci for a 10-day run) by irradiation of natural thorium with medium-energy protons followed by chemical isolation has been developed at the Institute for Nuclear Research of the Russian Academy of Sciences (INR RAS). Ac-225 with a small (~0.2%) impurity of Ac-227, which also forms under the irradiation, is appropriate as a mother radionuclide for Ac-225/Bi-213 generator. The literature describes generator systems Ac-225/Bi-213 based on both ion exchange and extraction chromatographic resins (Actinide Resin; UTEVA Resin, Triskem Int.). The initial activity of Ac-225 has been so far limited by the capabilities of its production as well as the radiation resistance of the sorbents used in the generator. The most studied is the Ac-225/Bi-213 generator based on a cation exchange resin of the type AG MP-50 (BioRad), and clinical tests are carried out using such generators. Systems of so-called multicolumn selective inversion generators (MSIG) was developed at PNNL, USA. Significant drawbacks of the existing generators are that they are designed for a radiochemically pure parent radionuclide with initial activity below 100 mCi. Two unique Ac-225/Bi-213 generators have been developed in INR RAS. The first one – termoxide inverse generator (TIG) – is based on a modified inorganic sorbent made from annealed zirconium and yttrium oxides [1]. The other one named «Afrabis» is a two-column generator where Ac-225 is firmly retained by Actinide Resin on the first column, and Bi-213 is accumulated and concentrated due to the separation and decay of the short-lived Fr-221 on the second column with AG MP-50 resin [2]. These generator systems demonstrate high radiation resistance, express production of Bi-213 and reliability.