Unraveling Interaction of Rhenium-188 Microspheres with Primary Hepatic Cancer Cell: A Breakthrough Study.

Abstract

Introduction: Hepatocellular carcinoma is a prevalent contributor to global mortality rates. The main palliative treatments are trans-arterial chemoembolization and selective intra-arterial radionuclide therapy. Methods: A novel freeze-dried nonradioactive microsphere kit formulation has been developed, and the behavior and therapeutic potential of ¹⁸⁸Re microspheres have been assessed. The microspheres were labeled with fluorescein isothiocyanate (FITC) and ¹⁸⁸ReO₄^-. The uptake of FITC microspheres by HepG2 cells was examined at various time intervals. The impact of ¹⁸⁸Re microspheres on cell viability and the mode of cell death were investigated with HepG2 cells using MTT and Annexin FITC-V/propidium iodide (PI) apoptosis assay. Results: The labeling efficiency of microspheres was more than 99% with FITC and ¹⁸⁸ReO₄^-. The maximum uptake of FITC microspheres by HepG2 cells was achieved at 6 h. The exposure to ¹⁸⁸Re microspheres has shown a decrease in cellular viability from 77.81% ± 0.015% to 42.03% ± 0.148% at 192 h of incubation (∼11 half-lives). The cellular uptake of ¹⁸⁸Re microspheres was 0.255-0.901 MBq. These values were concordant with Annexin FITC-V/PI apoptosis assay. At 192 h, 53.28% ± 0.01% of cells entered the apoptotic phase after treatment with ¹⁸⁸Re microspheres, and only 39.34% ± 0.02% of cells remained viable. However, in the cells treated with ¹⁸⁸ReO₄^- alone, 74.86% ± 0.005% of cells were viable, and only 24.75% ± 0.577% of cells were in the early apoptotic phase at 192 h. Conclusion: The data revealed that ¹⁸⁸Re microspheres treatment led to significant growth inhibition in HepG2 cells compared with ¹⁸⁸ReO₄^-.