High and low let particle-emitting isotopes for therapy: A comparison of cytotoxicity and dose-rate effects

A major consideration when using low Linear Energy Transfer (LET) isotopes such as beta emitters in radioimmunotherapy is repair of sublethal damage when radiation is delivered at low dose-rates. Clinical studies of beta emitters linked to MoAbs to date have reported tumor dose rates estimated to range from 0.01-0.1 Gy/hour. Since cytotoxicity can be markedly reduced as the dose-rate decreases for low LET isotopes, we have examined Pb-212 complexed with DTPA, which is less dose-rate dependent, in comparison to Y-90 -DTPA in cytotoxicity studies with Chinese hamster cells. Clonogenic survival studies revealed no dose-rate effect for Pb-212 over a range of 0.1-0.6 Gy/h. When compared to Y-90, Pb-212 showed a 20-fold higher toxicity at the 10% survival level at a dose-rate of 0.6 Gy/h. The use of high LET radionuclides such as Pb-212 should be considered for radioimmunotherapy, particularly where radiation dose to the tumor is delivered at low dose rates