PHB Imaging Group, AstraZeneca, 19F22 Mereside, Alderley Park, Macclesfield, SK10 4TG, UK.
Mol Imaging Biol. 2012 Jun;14(3):355-65. doi: 10.1007/s11307-011-0504-4.
The aim of this study is to assess the variability of 2-deoxy-2-[(18)F]fluoro-D: -glucose ([(18)F]-FDG) and 3'-deoxy-3'-[(18)F]-fluorothymidine ([(18)F]-FLT) uptake in pre-clinical tumor models and examine the relationship between imaging data and related histological biomarkers.
[(18)F]-FDG and [(18)F]-FLT studies were carried out in nine human tumor xenograft models in mice. A selection of the models underwent histological analysis for endpoints relevant to radiotracer uptake. Comparisons were made between in vitro uptake, in vivo imaging, and ex vivo histopathology data using quantitative and semi-quantitative analysis.
In vitro data revealed that [1-(14)C]-2-deoxy-D: -glucose ([(14)C]-2DG) uptake in the tumor cell lines was variable. In vivo, [(18)F]-FDG and [(18)F]-FLT uptake was highly variable across tumor types and uptake of one tracer was not predictive for the other. [(14)C]-2DG uptake in vitro did not predict for [(18)F]-FDG uptake in vivo. [(18)F]-FDG SUV was inversely proportional to Ki67 and necrosis levels and positively correlated with HKI. [(18)F]-FLT uptake positively correlated with Ki67 and TK1.
When evaluating imaging biomarkers in response to therapy, the choice of tumor model should take into account in vivo baseline radiotracer uptake, which can vary significantly between models.
本研究旨在评估 2-脱氧-2-[(18)F]氟代-D: -葡萄糖 ([(18)F]-FDG) 和 3'-脱氧-3'-[(18)F]氟代胸苷 ([(18)F]-FLT) 在临床前肿瘤模型中的摄取变异性，并研究影像学数据与相关组织学生物标志物之间的关系。
在 9 种小鼠人肿瘤异种移植模型中进行了 [(18)F]-FDG 和 [(18)F]-FLT 研究。选择部分模型进行与放射性示踪剂摄取相关的终点的组织学分析。使用定量和半定量分析比较体外摄取、体内成像和体外组织病理学数据。
体外数据显示，肿瘤细胞系中 [1-(14)C]-2-脱氧-D: -葡萄糖 ([(14)C]-2DG) 的摄取存在差异。在体内，不同肿瘤类型之间 [(18)F]-FDG 和 [(18)F]-FLT 的摄取差异很大，一种示踪剂的摄取不能预测另一种示踪剂的摄取。体外 [(14)C]-2DG 摄取不能预测体内 [(18)F]-FDG 摄取。[(18)F]-FDG SUV 与 Ki67 和坏死水平呈反比，与 HKI 呈正相关。[(18)F]-FLT 摄取与 Ki67 和 TK1 呈正相关。
在评估治疗反应中的成像生物标志物时，应考虑肿瘤模型的体内基线放射性示踪剂摄取，因为不同模型之间的摄取差异可能很大。
