α-Particle-induced DNA damage tracks in peripheral blood mononuclear cells of [(223)Ra]RaCl(2)-treated prostate cancer patients

PURPOSE: One therapy option for prostate cancer patients with bone metastases is the use of [(223)Ra]RaCl(2). The α-emitter (223)Ra creates DNA damage tracks along α-particle trajectories (α-tracks) in exposed cells that can be revealed by immunofluorescent staining of γ-H2AX+53BP1 DNA double-strand break markers. We investigated the time- and absorbed dose-dependency of the number of α-tracks in peripheral blood mononuclear cells (PBMCs) of patients undergoing their first therapy with [(223)Ra]RaCl(2). METHODS: Multiple blood samples from nine prostate cancer patients were collected before and after administration of [(223)Ra]RaCl(2), up to 4 weeks after treatment. γ-H2AX- and 53BP1-positive α-tracks were microscopically quantified in isolated and immuno-stained PBMCs. RESULTS: The absorbed doses to the blood were less than 6 mGy up to 4 h after administration and maximally 16 mGy in total. Up to 4 h after administration, the α-track frequency was significantly increased relative to baseline and correlated with the absorbed dose to the blood in the dose range < 3 mGy. In most of the late samples (24 h – 4 weeks after administration), the α-track frequency remained elevated. CONCLUSION: The γ-H2AX+53BP1 assay is a potent method for detection of α-particle-induced DNA damages during treatment with or after accidental incorporation of radionuclides even at low absorbed doses. It may serve as a biomarker discriminating α- from β-emitters based on damage geometry. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00259-020-05170-6.