An investigation of calcium carbonate core-shell particles for incorporation of 225Ac and sequester of daughter radionuclides: in vitro and in vivo studies

Abstract

Alpha therapy provides an outstanding prospect in the treatment of recalcitrant and micrometastatic cancers. However, side effects on the normal tissues and organs (especially, kidneys) due to the release of daughter isotopes from α-emitters remain a bottleneck. In this work, calcium carbonate core-shell particles of different sizes were considered as isotope carriers for encapsulation of ²²⁵Ac (highly powerful alpha-emitter that generates 4 net alpha particle isotopes in a short decay chain) in order to achieve in vitro and in vivo retention of ²²⁵Ac and its daughter isotopes. According to the in vitro studies, the developed calcium carbonate core-shell particles were able to retain ²²⁵Ac and its daughter isotopes (²²¹Fr and ²¹³Bi) exhibited good stability in biological media and dose-dependent biocompatibility (over 30 d). The SPECT imaging demonstrated the size-dependent distribution of ²²⁵Ac-doped core-shell particles. Further, in vivo studies confirmed the high retention efficiency of calcium carbonate core-shell particles, which was demonstrated in normal Wistar rats (up to 10 d). Interestingly, the radioactivity accumulation in kidney and urine was significantly less for encapsulated ²²⁵Ac than in case of non-encapsulated form of ²²⁵Ac (²²⁵Ac conjugated with albumin), indicating the absence of radioisotope leakage from the developed particles. Thus, our study validates the application of ²²⁵Ac-doped core-shell particles to sequester α-emitter (²²⁵Ac) and its decay products in order to reduce their systemic toxicity during alpha therapy.

Keywords: Actinium; Alpha therapy; Calcium carbonate; Core-shell particles; Daughter isotopes; Radiolabeling; Radionuclide retention; SPECT; in vivo biodistribution.