Repair of a-particle-induced DNA damage in peripheral blood mononuclear cells after internal ex vivo irradiation with \(^{223}\)Ra
Please always quote using this URN: urn:nbn:de:bvb:20-opus-324557
- Purpose As α-emitters for radiopharmaceutical therapies are administered systemically by intravenous injection, blood will be irradiated by α-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 [\(^{223}\)Ra]RaCl2. Methods Blood samples of ten volunteers were irradiated by adding [\(^{223}\)Ra]RaCl2 solution with different activityPurpose As α-emitters for radiopharmaceutical therapies are administered systemically by intravenous injection, blood will be irradiated by α-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 [\(^{223}\)Ra]RaCl2. Methods Blood samples of ten volunteers were irradiated by adding [\(^{223}\)Ra]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 γ-H2AX α-tracks were counted. The time-dependent decrease in α-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 α-tracks were significantly increased compared to baseline at all time points. Compared to the corresponding d-samples, the α-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.…
Author: | Lukas Göring, Sarah Schumann, Jessica Müller, Andreas K. BuckORCiD, Matthias Port, Michael Lassmann, Harry Scherthan, Uta EberleinORCiD |
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URN: | urn:nbn:de:bvb:20-opus-324557 |
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 |
Year of Completion: | 2022 |
Volume: | 49 |
Issue: | 12 |
Pagenumber: | 3981-3988 |
Source: | European Journal of Nuclear Medicine and Molecular Imaging (2022) 49:12, 3981-3988. DOI: 10.1007/s00259-022-05860-3 |
DOI: | https://doi.org/10.1007/s00259-022-05860-3 |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Tag: | DSB damage; irradiation; repair; α-Particle; γ-H2AX |
Release Date: | 2024/03/08 |
Licence (German): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |