Repair of α-particle-induced DNA damage in peripheral blood mononuclear cells after internal ex vivo irradiation with 223Ra

Purpose As alpha-emitters for radiopharmaceutical therapies are administered systemically by intravenous injection, blood will be irradiated by alpha-particles that induce clustered DNA double-strand breaks (DSBs). Here, we investigated the induction and repair of DSB damage in peripheral blood mononuclear cells (PBMCs) as a function of the absorbed dose to the blood following internal ex vivo irradiation with [Ra-223]RaCl2. Methods Blood samples of ten volunteers were irradiated by adding [Ra-223]RaCl2 solution with different activity concentrations resulting in absorbed doses to the blood of 3 mGy, 25 mGy, 50 mGy and 100 mGy. PBMCs were isolated, divided in three parts and either fixed directly (d-samples) or after 4 h or 24 h culture. After immunostaining, the induced gamma-H2AX alpha-tracks were counted. The time-dependent decrease in a-track frequency was described with a model assuming a repair rate R and a fraction of non-repairable damage Q. Results For 25 mGy, 50 mGy and 100 mGy, the numbers of alpha-tracks were significantly increased compared to baseline at all time points. Compared to the corresponding d-samples, the alpha-track frequency decreased significantly after 4 h and after 24 h. The repair rates R were (0.24 +/- 0.05) h(-1) for 25 mGy, (0.16 +/- 0.04) h(-1) for 50 mGy and (0.13 +/- 0.02) h(-1) for 100 mGy, suggesting faster repair at lower absorbed doses, while Q-values were similar. Conclusion The results obtained suggest that induction and repair of the DSB damage depend on the absorbed dose to the blood. Repair rates were similar to what has been observed for irradiation with low linear energy transfer.

Automated summary

This study investigated the induction and repair of DSB damage in peripheral blood mononuclear cells following internal and external irradiation. The results suggest that the induction and repair of DSB damage depend on the absorbed dose, with similar repair rates as low linear energy transfer irradiation.