DNA Damage and Repair in PBMCs after Internal Ex Vivo Irradiation with [223Ra]RaCl2 and [177Lu]LuCl3 Mixtures
Abstract
:1. Introduction
2. Results
2.1. Dosimetry
2.2. RIF Induction
2.3. α-Track Induction
2.4. DNA Damage Repair of Focal DSB Damage: RIF
2.5. DNA Damage Repair of α-Tracks
3. Discussion
4. Materials and Methods
4.1. Internal Irradiation, Preparation of Blood Samples and Blood Dosimetry
4.2. Immunofluorescent Staining and Evaluation of DNA Damage
4.3. Modelling of DNA Damage Repair
4.4. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Mixing Ratio | Absorbed Dose to the Blood (mGy) | Average Number of α-Tracks in 100 Cells | Average Number of RIF per Cell | |||||
---|---|---|---|---|---|---|---|---|
0 (baseline) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
25% 223Ra and 75% 177Lu | 25.3 (23.6–26.1) | 75.7 (70.8–80.5) | 5.9 (2.0–9.0) | 2.8 (0.0–4.0) | 0.6 (0.0–2.0) | 1.0 (0.7–1.4) | 0.4 (0.0–0.7) | 0.1 (−0.1–0.5) |
50% 223Ra and 50% 177Lu | 50.6 (46.6–53.3) | 51.3 (47.1–57.0) | 8.1 (4.0–12.0) | 4.7 (2.0–8.0) | 1.0 (0.0–2.0) | 0.8 (0.4–1.3) | 0.4 (0.1–0.8) | 0.2 (−0.1–0.5) |
75% 223Ra and 25% 177Lu | 76.5 (73.2–79.8) | 26.7 (24.9–28.5) | 13.1 (9.0–18.0) | 4.9 (1.0–9.0) | 0.7 (0.0–2.0) | 0.7 (0.4–1.1) | 0.4 (0.2–0.8) | 0.2 (−0.1–0.5) |
β-Part | Persisting RIF (%) | Fit Parameter | ||||
---|---|---|---|---|---|---|
4 h | 24 h | N0,β | Rβ (h−1) | Qβ | r2 | |
25% 177Lu | 59 | 35 | 0.65 ± 0.06 | 0.25 ± 0.12 | 0.35 ± 0.10 | 0.49 |
50% 177Lu | 47 | 47 | 0.81 ± 0.08 | 0.29 ± 0.13 | 0.23 ± 0.10 | 0.53 |
75% 177Lu | 40 | 14 | 0.98 ± 0.07 | 0.31 ± 0.09 | 0.14 ± 0.07 | 0.75 |
α-Part | Persisting α-Tracks (%) | Fit Parameter | ||||
---|---|---|---|---|---|---|
4 h | 24 h | N0,α | Rα (h−1) | Qα | r2 | |
25% 223Ra | 47 | 10 | 5.90 ± 0.48 | 0.22 ± 0.07 | 0.10 ± 0.09 | 0.69 |
50% 223Ra | 58 | 12 | 8.10 ± 0.59 | 0.16 ± 0.05 | 0.10 ± 0.09 | 0.73 |
75% 223Ra | 37 | 5 | 13.45 ± 0.78 | 0.26 ± 0.05 | 0.05 ± 0.06 | 0.82 |
Mixing Ratio | [223Ra]RaCl2 | α-Dose | [177Lu]LuCl3 | β-Dose |
---|---|---|---|---|
25% 223Ra and 75% 177Lu | 1.7 kBq/mL | 25 mGy | 0.94 MBq/mL | 75 mGy |
50% 223Ra and 50% 177Lu | 3.5 kBq/mL | 50 mGy | 0.63 MBq/mL | 50 mGy |
75% 223Ra and 25% 177Lu | 5.2 kBq/mL | 75 mGy | 0.31 MBq/mL | 25 mGy |
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Strobel, I.; Schumann, S.; Müller, J.; Buck, A.K.; Port, M.; Lassmann, M.; Eberlein, U.; Scherthan, H. DNA Damage and Repair in PBMCs after Internal Ex Vivo Irradiation with [223Ra]RaCl2 and [177Lu]LuCl3 Mixtures. Int. J. Mol. Sci. 2024, 25, 8629. https://doi.org/10.3390/ijms25168629
Strobel I, Schumann S, Müller J, Buck AK, Port M, Lassmann M, Eberlein U, Scherthan H. DNA Damage and Repair in PBMCs after Internal Ex Vivo Irradiation with [223Ra]RaCl2 and [177Lu]LuCl3 Mixtures. International Journal of Molecular Sciences. 2024; 25(16):8629. https://doi.org/10.3390/ijms25168629
Chicago/Turabian StyleStrobel, Isabella, Sarah Schumann, Jessica Müller, Andreas K. Buck, Matthias Port, Michael Lassmann, Uta Eberlein, and Harry Scherthan. 2024. "DNA Damage and Repair in PBMCs after Internal Ex Vivo Irradiation with [223Ra]RaCl2 and [177Lu]LuCl3 Mixtures" International Journal of Molecular Sciences 25, no. 16: 8629. https://doi.org/10.3390/ijms25168629