Radiopharmaceuticals used for diagnosis or therapy induce DNA strand breaks, which may be detectable by single-cell gel electrophoresis (called comet assay). Blood was taken from patients before and at different time points after treatment with radiopharmaceuticals; blood cells were investigated by the comet assay using the percentage of DNA in the tail as the critical parameter. Whereas [225Ac]Ac-prostate-specific membrane antigen (PSMA)-617 alpha therapy showed no difference relative to the blood sample taken before treatment, beta therapy with [177Lu]Lu-PSMA-617 3 h post-injection revealed a small but significant increase in DNA strand breaks. In blood of patients who underwent positron emission tomography (PET) with either [18F]2-fluor-2-deoxy-D-glucose (FDG) or [68Ga]Ga-PSMA-11, an increase of DNA migration determined by the comet assay was not found when analysed at different time points (2-70 min) after intravenous tracer injection. Human whole blood was incubated with the targeted clinically relevant therapeutic radiopharmaceuticals [225Ac]Ac-PSMA-617, [177Lu]Lu-PSMA-617 and [90Y]Y-DOTA(0)-Phe(1)-Tyr(3)-octreotide (DOTA-TOC) at different activity concentrations (kBq/ml) for 5 days and then analysed by the comet assay. DNA damage increased with higher concentrations of all radiolabeled compounds tested. [177Lu]Lu-PSMA-617 caused higher blood cell radiotoxicity than equal activity concentrations of [90Y]Y-DOTA-TOC. Likewise, whole human blood was exposed to the positron emitters [18F]FDG and [68Ga]Ga-PSMA-11 in vitro for 24 h with activity concentrations ranging between 5 and 40 MBq/ml. The same activity concentration dependent elevated DNA migration was observed for both compounds although decay energies are different. This study demonstrated that the amount of DNA damage detected by the comet assay in whole human blood is similar among different positron emitters and divergent by a factor of 200 between alpha particles and beta radiation.

中文翻译：

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彗星试验评估了放射性药物在人全血中造成的DNA损伤。

用于诊断或治疗的放射性药物会诱导DNA链断裂，这可以通过单细胞凝胶电泳（称为彗星试验）来检测。在用放射性药物治疗之前和之后的不同时间点从患者那里采血；通过彗星试验研究血细胞，使用尾巴中DNA的百分比作为关键参数。[225Ac] Ac-前列腺特异性膜抗原（PSMA）-617α治疗与治疗前采集的血样相比无差异，而注射[177Lu] Lu-PSMA-617的β治疗在注射后3 h表现出较小但DNA链断裂的显着增加。在接受[18F] 2-氟-2-脱氧-D-葡萄糖（FDG）或[68Ga] Ga-PSMA-11进行正电子发射断层扫描（PET）的患者的血液中，在静脉示踪剂注射后的不同时间点（2-70分钟）进行分析时，未发现通过彗星分析确定的DNA迁移增加。将人类全血与靶向的临床相关治疗性放射性药物[225Ac] Ac-PSMA-617，[177Lu] Lu-PSMA-617和[90Y] Y-DOTA（0）-Phe（1）-Tyr（3）-以不同活性浓度（kBq / ml）的奥曲肽（DOTA-TOC）放置5天，然后通过彗星试验进行分析。随着测试的所有放射性标记化合物浓度的升高，DNA损伤也会增加。[177Lu] Lu-PSMA-617引起的血细胞放射毒性高于[90Y] Y-DOTA-TOC的相同活性浓度。同样，全血在体外暴露于正电子发射体[18F] FDG和[68Ga] Ga-PSMA-11，历时24 h，活性浓度在5和40 MBq / ml之间。尽管衰变能量不同，但两种化合物均观察到相同活性浓度依赖性的DNA迁移升高。这项研究表明，通过彗星测定法在全人类血液中检测到的DNA损伤量在不同的正电子发射体之间相似，并且在α粒子和β辐射之间的差异为200倍。