Eberlein Uta, Scherthan Harry, Bluemel Christina, Peper Michel, Lapa Constantin, Buck Andreas Konrad, Port Matthias, Lassmann Michael
Department of Nuclear Medicine, University of Würzburg, Germany; and.
Bundeswehr Institute of Radiobiology affiliated to the University of Ulm, Munich, Germany.
J Nucl Med. 2016 Feb;57(2):173-9. doi: 10.2967/jnumed.115.164814. Epub 2015 Nov 12.
The aim of the study was to investigate DNA double-strand break (DSB) formation and its correlation to the absorbed dose to the blood in patients with surgically treated differentiated thyroid cancer undergoing their first radioiodine therapy for remnant ablation.
Twenty patients were included in this study. At least 7 peripheral blood samples were obtained before and between 0.5 and 120 h after administration of radioiodine. From the time-activity curves of the blood and the whole body, residence times for the blood self-irradiation and the irradiation from the whole body were determined. Peripheral blood lymphocytes were isolated, ethanol-fixed, and subjected to immunofluorescence staining for colocalizing γ-H2AX/53BP1 DSB-marking foci. The average number of DSB foci per cell per patient sample was analyzed as a function of the absorbed dose to the blood and compared with an in vitro calibration curve for (131)I and (177)Lu established previously in our institution.
The average number of radiation-induced foci (RIF) per cell increased over the first 3 h after radionuclide administration and decreased thereafter. A linear fit from 0 to 2 h as a function of the absorbed dose to the blood agreed with our in vitro calibration curve. At later time points, RIF numbers diminished, along with dropping dose rates, indicating progression of DNA repair. Individual patient data were characterized by a linear dose-dependent increase and a biexponential response function describing a fast and a slow repair component.
With the experimental results and model calculations presented in this work, a dose-response relationship is demonstrated, and an analytic function describing the time course of the in vivo damage response after internal irradiation of patients with (131)I is established.
本研究的目的是调查接受首次放射性碘治疗以清除残留甲状腺组织的手术治疗分化型甲状腺癌患者中DNA双链断裂（DSB）的形成及其与血液吸收剂量的相关性。
本研究纳入了20名患者。在给予放射性碘之前以及给药后0.5至120小时之间至少采集7份外周血样本。根据血液和全身的时间-活度曲线，确定血液自身照射和全身照射的停留时间。分离外周血淋巴细胞，用乙醇固定，并进行免疫荧光染色以共定位γ-H2AX/53BP1 DSB标记灶。分析每位患者样本中每个细胞的DSB灶平均数量与血液吸收剂量的函数关系，并与我们机构先前建立的针对（131）I和（177）Lu的体外校准曲线进行比较。
每个细胞的辐射诱导灶（RIF）平均数量在放射性核素给药后的前3小时内增加，此后减少。从0到2小时作为血液吸收剂量函数的线性拟合与我们的体外校准曲线一致。在随后的时间点，RIF数量随着剂量率下降而减少，表明DNA修复在进行。个体患者数据的特征是呈线性剂量依赖性增加以及具有描述快速和缓慢修复成分的双指数响应函数。
通过本研究中呈现的实验结果和模型计算，证明了剂量-反应关系，并建立了描述（131）I体内照射后患者体内损伤反应时间进程的解析函数。
