An electrochemical generator for the continual supply of 213Bi from 225Ac for use in targeted alpha therapy applications

Abstract

Bismuth-213 is a radionuclide of interest for targeted alpha therapy and is supplied via a radiochemical generator system through the decay of ²²⁵Ac. Radionuclide generators employ longer lived "parent" radionuclides to routinely supply shorter-lived "daughter" radionuclides. The traditional ²²⁵Ac/²¹³Bi radiochemical generator relies on an organic cation exchange resin where ²²⁵Ac binds to the resin and ²¹³Bi is routinely eluted. These resins degrade when they absorb large doses of ionizing radiation (>1 × 10⁶ Gy/mg), which has been observed when the loading activity of ²²⁵Ac exceeds 2.59*10⁹ Bq (70 mCi). Herein we report the development of an electrochemical generator for the supply of ²¹³Bi that has the potential to overcome this limitation. Bismuth-213 spontaneously electrodeposits onto nickel foils in 0.1 M hydrochloric acid at 70 °C. Using this method, we were able to plate an average of 73 ± 4 % of the ²¹³Bi in solution and obtain a final ²¹³Bi recovery of 65 ± 8 % in 0.1 M citrate pH 4.5 via reverse electrolysis using titanium as the cathode. The recovered ²¹³Bi had an average radiochemical purity of >99.8 % and was successfully used to radiolabel DOTATATE with an average radiochemical yield of 85.1 % (not optimized).

Keywords: Actinium-225; Bismuth-213; Electrochemistry; Radiochemistry; Radionuclide generator; Targeted alpha therapy.