Radiobiological comparison of holmium-166 and yttrium-90 for hepatocellular carcinoma treatment in vitro

Radioembolization for hepatocellular carcinoma uses microspheres radiolabeled with yttrium-90 or holmium-166, yet their radiobiological effectiveness has not been directly compared, leaving radionuclide selection uninformed by biological considerations. We assessed the survival and DNA damage induction following 1.5 or 2.5 Gy of [166Ho]Ho-DOTA or [90Y]Y-DOTA delivered over 24 h on three human hepatocellular carcinoma cell lines. Both radionuclides led to a similar, dose-dependent reduction of survival in all cell lines, with a modest but nonsignificant trend towards increased toxicity for [166Ho]Ho-DOTA. Notably, [166Ho]Ho-DOTA induced fewer, but larger DNA damage foci at earlier time points during irradiation, suggesting subtle differences in damage complexity or repair kinetics. These findings suggest that when delivering the same absorbed dose over 24 h, [166Ho]Ho-DOTA and [90Y]Y-DOTA demonstrate comparable cytotoxicity in vitro. These findings imply that in clinical settings, additional factors such as total injected activity and microsphere composition and biodistribution likely exert greater influence on treatment efficacy than radionuclide choice alone.