An alternative radiochemical separation strategy for isolation of Ac and Ra isotopes from high energy proton irradiated thorium targets for further application in Targeted Alpha Therapy (TAT)

Abstract

Targeted Alpha Therapy (TAT) has shown very high potential for the treatment of cancers that were not responsive to other therapy options (e.g., β^- therapy and chemotherapy). The main constraint to the widespread use of TAT in clinics is the limited availability of alpha-emitting radionuclides. One of the most promising candidates for TAT is ²²⁵Ac (t_1/2 = 9.92 days), which can be used directly in combination with selective biomolecules (e.g., antibodies, peptides, etc.) or be a generator source of ²¹³Bi (t_1/2 = 45.6 min), another shorter-lived TAT radionuclide. Several strategies are currently under investigation to increase the supply of ²²⁵Ac. One of the most attractive options is the irradiation of natural thorium-232 targets with high-energy protons (≥100 MeV). However, there are several challenges associated with this production method including the development of an efficient radiochemical purification method. During irradiation of natural thorium with proton energy above 100 MeV, several Ra isotopes (^223,224,225Ra) are produced. ²²³Ra (t_1/2 = 11.43 days) is used for the treatment of bone metastases and can also be used as a generator source for ²¹¹Pb. Additionally, ²²⁵Ra (t_1/2 = 14.9 days) can be a valuable source of isotopically pure ²²⁵Ac. In the present work, we address the radiochemical separation aspects of isolating Ac and Ra isotopes from irradiated thorium targets.

Keywords: (223/225)Ra; (225)Ac; Cation exchange; DN resin; Natural thorium metal; SR resin; Spallation; Thorium chelation; Trichloroacetic acid.