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

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 alpha-emitters remain a bottleneck. In this work, calcium carbonate core-shell particles of different sizes were considered as isotope carriers for encapsulation of Ac-225 (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 Ac-225 and its daughter isotopes. According to the in vitro studies, the developed calcium carbonate core-shell particles were able to retain Ac-225 and its daughter isotopes (Fr-221 and Bi-213) exhibited good stability in biological media and dose-dependent biocompatibility (over 30 d). The SPECT imaging demonstrated the size-dependent distribution of Ac-225-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 Ac-225 than in case of non-encapsulated form of Ac-225 (Ac-225 conjugated with albumin), indicating the absence of radioisotope leakage from the developed particles. Thus, our study validates the application of Ac-225-doped core-shell particles to sequester alpha-emitter (Ac-225) and its decay products in order to reduce their systemic toxicity during alpha therapy.

Automated summary

Alpha therapy has promising potential in treating aggressive cancers, but the side effects on normal tissues and organs have remained a challenge. This study used calcium carbonate core-shell particles to encapsulate Ac-225 and its daughter isotopes, demonstrating good retention and stability in biological environments. The in vivo studies in rats showed high retention efficiency and reduced radioactivity accumulation in the kidneys and urine, suggesting a possible strategy for minimizing systemic toxicity during alpha therapy.