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

Please always quote using this URN: urn:nbn:de:bvb:20-opus-265462
  • 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 withPurpose 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.show moreshow less

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Metadaten
Author: S. Schumann, U. Eberlein, C. Lapa, J. Müller, S. Serfling, M. Lassmann, H. Scherthan
URN:urn:nbn:de:bvb:20-opus-265462
Document Type:Journal article
Faculties:Medizinische Fakultät / Klinik und Poliklinik für Nuklearmedizin
Language:English
Parent Title (English):European Journal of Nuclear Medicine and Molecular Imaging
ISSN:1619-7089
Year of Completion:2021
Volume:48
Issue:9
Pagenumber:2761-2770
Source:European Journal of Nuclear Medicine and Molecular Imaging 2021, 48(9):2761-2770. DOI: 10.1007/s00259-020-05170-6
DOI:https://doi.org/10.1007/s00259-020-05170-6
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=33537837
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:53BP1; DNA damage; [\(^{223}\)Ra]RaCl\(_{2}\); biokinetics; dosimetry; nuclear medicine; prostate cancer; α-Emitter; γ-H2AX
Release Date:2022/09/20
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International