Department of Radiology, University Hospital Erlangen, Erlangen, Germany.
Eur J Nucl Med Mol Imaging. 2012 Nov;39(11):1712-9. doi: 10.1007/s00259-012-2201-1. Epub 2012 Aug 2.
The purpose of this study was to evaluate DNA double-strand breaks (DSBs) in blood lymphocytes of patients undergoing positron emission tomography (PET)/CT using γ-H2AX immunofluorescence microscopy and to differentiate between (18)F-fluorodeoxyglucose (FDG) and CT-induced DNA lesions.
This study was approved by the local Ethics Committee and complies with Health Insurance Portability and Accountability Act (HIPAA) requirements. After written informed consent was obtained, 33 patients underwent whole-body (18)F-FDG PET/CT (3 MBq/kg body weight, 170/100 reference mAs at 120 kV). The FDG PET and CT portions were performed as an initial CT immediately followed by the PET. Blood samples were obtained before, at various time points following (18)F-FDG application and up to 24 h after the CT scan. Distinct foci representing DSBs were quantified in isolated lymphocytes using fluorescence microscopy after staining against the phosphorylated histone variant γ-H2AX.
The DSB values at the various time points were significantly different (p < 0.001). The median baseline level was 0.08/cell (range 0.06-0.12/cell). Peaks of radiation-induced DSBs were found 30 min after (18)F-FDG administration (median excess foci 0.11/cell, range 0.06-0.27/cell) and 5 min after CT (median excess foci 0.17/cell, range 0.05-0.54/cell). A significant correlation between CT-induced DSBs and dose length product was obtained (ρ = 0.898, p < 0.001). After 24 h DSB values were still slightly but significantly elevated (median foci 0.11/cell, range 0.10-0.14/cell, p = 0.003) compared to pre-exposure levels.
PET/CT-induced DSBs can be monitored using γ-H2AX immunofluorescence microscopy. Peak values may be obtained 30 min after (18)F-FDG injection and 5 min after CT. The radionuclide contributes considerably to the total DSB induction in this setting.
本研究旨在通过 γ-H2AX 免疫荧光显微镜评估正电子发射断层扫描（PET）/CT 检查中患者血液淋巴细胞的 DNA 双链断裂（DSB），并区分（18）F-氟脱氧葡萄糖（FDG）和 CT 引起的 DNA 损伤。
本研究获得了当地伦理委员会的批准，并符合健康保险流通与责任法案（HIPAA）的要求。在获得书面知情同意后，33 名患者接受了全身（18）F-FDG PET/CT（3 MBq/kg 体重，120 kV 时 170/100 参考 mAs）。FDG PET 和 CT 部分作为初始 CT 立即在 PET 之后进行。在（18）F-FDG 应用后和 CT 扫描后 24 小时内的不同时间点采集血液样本。用针对磷酸化组蛋白变体 γ-H2AX 的抗体对分离的淋巴细胞进行染色后，用荧光显微镜定量代表 DSB 的独特焦点。
各时间点的 DSB 值差异有统计学意义（p<0.001）。基线中位数水平为 0.08/细胞（范围 0.06-0.12/细胞）。在（18）F-FDG 给药后 30 分钟（中位数过量焦点 0.11/细胞，范围 0.06-0.27/细胞）和 CT 后 5 分钟（中位数过量焦点 0.17/细胞，范围 0.05-0.54/细胞）时发现了放射性诱导的 DSB 峰值。还获得了 CT 诱导的 DSB 与剂量长度乘积之间的显著相关性（ρ=0.898，p<0.001）。24 小时后，DSB 值仍略有但仍显著升高（中位数焦点 0.11/细胞，范围 0.10-0.14/细胞，p=0.003），与暴露前水平相比。
可以使用 γ-H2AX 免疫荧光显微镜监测 PET/CT 诱导的 DSB。（18）F-FDG 注射后 30 分钟和 CT 后 5 分钟可获得峰值值。在这种情况下，放射性核素对总 DSB 诱导有很大贡献。
