Schumann Sarah, Scherthan Harry, Frank Torsten, Lapa Constantin, Müller Jessica, Seifert Simone, Lassmann Michael, Eberlein Uta
Department of Nuclear Medicine, University of Würzburg, Oberdürrbacher Str. 6, 97080 Würzburg, Germany.
Bundeswehr Institute of Radiobiology affiliated to the University of Ulm, Neuherbergstraße 11, 80937 München, Germany.
Cancers (Basel). 2020 Feb 7;12(2):388. doi: 10.3390/cancers12020388.
The aim was to investigate the induction and repair of radiation-induced DNA double-strand breaks (DSBs) as a function of the absorbed dose to the blood of patients undergoing PET/CT examinations with [Ga]Ga-PSMA. Blood samples were collected from 15 patients before and at four time points after [Ga]Ga-PSMA administration, both before and after the PET/CT scan. Absorbed doses to the blood were calculated. In addition, blood samples with/without contrast agent from five volunteers were irradiated ex vivo by CT while measuring the absorbed dose. Leukocytes were isolated, fixed, and stained for co-localizing γ-H2AX+53BP1 DSB foci that were enumerated manually. In vivo, a significant increase in γ-H2AX+53BP1 foci compared to baseline was observed at all time points after administration, although the absorbed dose to the blood by Ga was below 4 mGy. Ex vivo, the increase in radiation-induced foci depended on the absorbed dose and the presence of contrast agent, which could have caused a dose enhancement. The CT-dose contribution for the patients was estimated at about 12 mGy using the ex vivo calibration. The additional number of DSB foci induced by CT, however, was comparable to the one induced by Ga. The significantly increased foci numbers after [Ga]Ga-PSMA administration may suggest a possible low-dose hypersensitivity.
目的是研究接受[镓]镓-PSMA PET/CT检查的患者血液中辐射诱导的DNA双链断裂(DSB)的诱导和修复情况,作为吸收剂量的函数。在15名患者接受[镓]镓-PSMA给药前及给药后四个时间点采集血样,PET/CT扫描前后均进行。计算血液的吸收剂量。此外,对5名志愿者含有/不含造影剂的血样在体外进行CT照射,同时测量吸收剂量。分离白细胞,固定并染色,以共定位手动计数的γ-H2AX+53BP1 DSB病灶。在体内,给药后所有时间点均观察到γ-H2AX+53BP1病灶与基线相比显著增加,尽管镓对血液的吸收剂量低于4 mGy。在体外,辐射诱导病灶的增加取决于吸收剂量和造影剂的存在,造影剂可能导致剂量增强。使用体外校准估计患者的CT剂量贡献约为12 mGy。然而,CT诱导的DSB病灶额外数量与镓诱导的相当。[镓]镓-PSMA给药后病灶数量显著增加可能提示可能存在低剂量超敏反应。