RT Journal Article SR Electronic T1 Are there differences in the DNA double-strand break induction in blood leukocytes of prostate cancer patients during Ga-68-PSMA diagnostics and Lu-177-PSMA therapy? JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1625 OP 1625 VO 60 IS supplement 1 A1 Sarah Schumann A1 Harry Scherthan A1 Constantin Lapa A1 Michael Lassmann A1 Uta Eberlein YR 2019 UL http://jnm.snmjournals.org/content/60/supplement_1/1625.abstract AB 1625Objectives: The aim of this study was to compare the induction of DNA double-strand breaks (DSBs) in peripheral blood leukocytes of prostate cancer patients one hour after administration of Ga-68-PSMA for diagnostics and Lu-177-PSMA for therapy. As biomarkers for DNA DSBs we used γ-H2AX and 53BP1. Methods: For the comparison of the DSB induction one hour after administration, 13 patients were included receiving (143±19) MBq of Ga-68-PSMA for diagnostics (group 1) and 16 patients receiving (5.9 ± 0.2) GBq Lu-177-PSMA for therapy (group 2). For dosimetry, blood samples were taken before the administration, nominally 15 min and 60 min thereafter, directly after the PET/CT scan and 90-120 min after the scan for group 1 and, for group 2, before the administration and nominally 1 h, 2 h, 3 h, 4 h, 24 h, 48 h and 96 h after administration. For the analysis of the biomarkers, leukocytes were isolated, ethanol fixed and immuno-stained with γ-H2AX and 53BP1 antibodies. The number of foci with co-localizing γ-H2AX and 53BP1 signals were counted manually in a fluorescence microscope. The number of radiation-induced foci (RIF) in each sample were calculated by subtraction of individual background foci. CT scan influences were excluded by only comparing the foci induction after 1h. The absorbed doses to the blood at this time point was calculated using the time-integrated activity coefficients (TIACs) for blood and the whole body of the patients. For the study, we compared the number of RIF, the absorbed dose, and the respective ratio. Results: The mean absorbed dose to the blood after 1 h was (1.79 ± 0.50) mGy for the Ga-68-PSMA patients and (17.34 ± 5.54) mGy for the Lu-177-PSMA patients. However, the number of RIF did not show a statistically significant difference between both patient groups at 1h after administration, with the RIF values being similar: (0.25±0.13) and (0.29±0.14) for Ga-68-PSMA and Lu-177-PSMA, respectively. The RIF values per absorbed dose, (0.13±0.08) mGy-1 for Ga-68 and (0.02±0.01) mGy-1 for Lu-177, showed a significant difference. Conclusion: The observed RIF values of this study show an in-vivo induction of DNA double strand breaks in peripheral leukocytes at very low absorbed doses to the blood (< 3mGy) during the first hour of a diagnostic procedure. Unexpectedly, this induction is similar to the values obtained during therapy, indicating that the induction of DNA DSBs might be different for very low absorbed doses compared to absorbed doses observed during therapies. Further studies in the very low dose range are needed to confirm our findings.