Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 13, Issue 22, Pages 25599-25610Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.1c02155
Keywords
local radionuclide therapy; actinium-225; core-shell particles; melanoma
Funding
- Russian Science Foundation [19-75-10010]
- Tomsk Polytechnic University Competitiveness Enhancement Program
- Russian Science Foundation [19-75-10010] Funding Source: Russian Science Foundation
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Ac-225-doped core-shell submicron CaCO3 particles coated with biocompatible polymers demonstrated radiochemical stability, effective retention of Ac-225 and its daughter isotopes, and significant accumulation in tumor area according to PET/CT analysis. Treatment with Ac-225-SPs resulted in prolonged survival and inhibition of tumor growth in melanoma models.
Actinium 225 (Ac-225) radiolabeled submicrometric core-shell particles (SPs) made of calcium carbonate (CaCO3) coated with biocompatible polymers [tannic acid-human serum albumin (TA/HSA)] have been developed to improve the efficiency of local alpha-radionuclide therapy in melanoma models (B16-F10 tumor-bearing mice). The developed Ac-225-SPs possess radiochemical stability and demonstrate effective retention of Ac-225 and its daughter isotopes. The SPs have been additionally labeled with zirconium-89 (Zr-89) 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 Zr-89-SPs in the tumor area is revealed for the whole investigation period, which correlates with the direct radiometry analysis after intratumoral administration of Ac-225-SPs. The histological analysis has revealed no abnormal changes in healthy tissue organs after treatment with Ac-225-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 Ac-225-SPs has resulted in prolonged survival compared to the control samples. Thus, our study validates the application of Ac-225-doped core-shell submicron CaCO3 particles for local alpha-radionuclide therapy.
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