Repair of α-particle-induced DNA damage in peripheral blood mononuclear cells after internal ex vivo irradiation with 223Ra,European Journal of Nuclear Medicine and Molecular Imaging

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Repair of α-particle-induced DNA damage in peripheral blood mononuclear cells after internal ex vivo irradiation with 223Ra
European Journal of Nuclear Medicine and Molecular Imaging ( IF 8.6 ) Pub Date : 2022-06-27 , DOI: 10.1007/s00259-022-05860-3
Lukas Göring ₁ , Sarah Schumann ₁ , Jessica Müller ₂ , Andreas K Buck ₁ , Matthias Port ₂ , Michael Lassmann ₁ , Harry Scherthan ₂ , Uta Eberlein ₁

Affiliation

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 [²²³Ra]RaCl₂.

Methods

Blood samples of ten volunteers were irradiated by adding [²²³Ra]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.

中文翻译：

223Ra体内离体照射后α粒子诱导的外周血单个核细胞DNA损伤的修复

目的

由于用于放射性药物治疗的 α 发射体通过静脉注射进行全身给药，因此血液将被 α 粒子照射，从而诱导成簇 DNA 双链断裂 (DSB)。在这里，我们研究了外周血单核细胞 (PBMC) 中 DSB 损伤的诱导和修复，作为使用 [ ²²³ Ra]RaCl ₂进行体内离体照射后血液吸收剂量的函数。

方法

^{通过添加具有不同活性浓度的[ 223} Ra]RaCl ₂溶液辐照十名志愿者的血样，导致对血液的吸收剂量为3 mGy、25 mGy、50 mGy和100 mGy。分离 PBMC，分为三部分并直接固定（d-样品）或在 4 小时或 24 小时培养后固定。免疫染色后，对诱导的 γ-H2AX α-轨道进行计数。α-轨道频率的时间依赖性下降是用一个假设修复率R和一部分不可修复的损伤Q的模型来描述的。

结果

对于 25 mGy、50 mGy 和 100 mGy，与所有时间点的基线相比，α 径迹的数量显着增加。与相应的d-样本相比，α-轨道频率在 4 小时后和 24 小时后显着降低。25 mGy的修复率 R 为 (0.24 ± 0.05) h ^−1，50 mGy 为 (0.16 ± 0.04) h ⁻¹和 100 mGy 为(0.13 ± 0.02) h ⁻¹，表明在较低吸收剂量下修复速度更快，而Q 值相似。