α-Particle-induced DNA damage tracks in peripheral blood mononuclear cells of [223Ra]RaCl2-treated prostate cancer patients
Sarah Schumann, Uta Eberlein, Constantin Lapa, Müller Jm, Sebastian E. Serfling, Michael Laßmann, Harry Scherthan
Abstract
Abstract 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.