α-Particle-induced DNA damage tracks in peripheral blood mononuclear cells of [\(^{223}\)Ra]RaCl\(_{2}\)-treated prostate cancer patients
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- 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.…
Autor(en): | S. Schumann, U. Eberlein, C. Lapa, J. Müller, S. Serfling, M. Lassmann, H. Scherthan |
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URN: | urn:nbn:de:bvb:20-opus-265462 |
Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
Institute der Universität: | Medizinische Fakultät / Klinik und Poliklinik für Nuklearmedizin |
Sprache der Veröffentlichung: | Englisch |
Titel des übergeordneten Werkes / der Zeitschrift (Englisch): | European Journal of Nuclear Medicine and Molecular Imaging |
ISSN: | 1619-7089 |
Erscheinungsjahr: | 2021 |
Band / Jahrgang: | 48 |
Heft / Ausgabe: | 9 |
Seitenangabe: | 2761-2770 |
Originalveröffentlichung / Quelle: | 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: | https://pubmed.ncbi.nlm.nih.gov/33537837 |
Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Freie Schlagwort(e): | 53BP1; DNA damage; [\(^{223}\)Ra]RaCl\(_{2}\); biokinetics; dosimetry; nuclear medicine; prostate cancer; α-Emitter; γ-H2AX |
Datum der Freischaltung: | 20.09.2022 |
Lizenz (Deutsch): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |