Calcium Carbonate Core–Shell Particles for Incorporation of ²²⁵Ac and Their Application in Local α-Radionuclide Therapy

Actinium-225 ( 225 Ac) radiolabeled submicrometric core–shell particles (SPs) made of calcium carbonate (CaCO 3 ) coated with biocompatible polymers [tannic acid–human serum albumin (TA/HSA)] have been developed to improve the efficiency of local α-radionuclide therapy in melanoma models (B16-F10 tumor-bearing mice). The developed 225 Ac-SPs possess radiochemical stability and demonstrate effective retention of 225 Ac and its daughter isotopes. The SPs have been additionally labeled with zirconium-89 ( 89 Zr) to perform the biodistribution studies using positron emission tomography–computerized tomography (PET/CT) imaging for 14 days after intratumoral injection. According to the PET/CT analysis, a significant accumulation of 89 Zr-SPs in the tumor area is revealed for the whole investigation period, which correlates with the direct radiometry analysis after intratumoral administration of 225 Ac-SPs. The histological analysis has revealed no abnormal changes in healthy tissue organs after treatment with 225 Ac-SPs (e.g., no acute pathologic findings are detected in the liver and kidneys). At the same time, the inhibition of tumor growth has been observed as compared with control samples [nonradiolabeled SPs and phosphate-buffered saline (PBS)]. The treatment of mice with 225 Ac-SPs has resulted in prolonged survival compared to the control samples. Thus, our study validates the application of 225 Ac-doped core–shell submicron CaCO 3 particles for local α-radionuclide therapy.