Assessment of Tumor Proliferation after Anti-tumor Therapy by Thymidine Kinase 1 Activity with Nuclear Medicine Technique

目的：3'-脱氧-3'-[^<18>F - flt]氟胸腺嘧啶（^<18>F- flt）是一种正电子发射断层扫描（PET）示踪剂，被细胞摄取并被胸腺嘧啶激酶1磷酸化，与细胞增殖密切相关。本研究的目的是评估^< 18b> F-FLT作为肿瘤增殖标志物的作用。方法：SCCVII、PANC-1、LS174T和HeLa四种细胞系在体内表现出不同的生长速度。将^<18 b> F-FLT的肿瘤摄取与移植了这些细胞的小鼠的肿瘤加倍时间进行比较。在20 Gy照射后6小时至7天，检测了x射线照射对荷瘤小鼠^<18>F-FLT、^<18> f -氟-2-脱氧-d -葡萄糖（^<18>F-FDG）、^ 3h -甲基胸腺嘧啶（^3H-Thd）、^<14> c -2-脱氧-d -葡萄糖（^<14>C-DG）摄取的影响。光动力治疗后24小时检测肿瘤对每种放射性药物的摄取情况。静脉给药1小时后测定肿瘤对放射性药物的摄取情况。结果：4个细胞系中F-FLT的摄取与倍增时间无关。x射线照射后6小时，肿瘤对^<18 b> F-FLT和^3H-Thd的摄取显著减少。然而，^<18>的F-FDG和^<14>的C-DG的吸收量直到照射后3天才减少。光动力治疗减少了治疗后24小时^<18>的F-FDG和^3H-Thd的摄取，但没有减少^<18>的F-FDG和^<14>的C-DG的摄取。结论：^<18>F-FDG比^<18>F-FDG对放射治疗或光动力治疗反应的评价更敏感。

Objectives : 3'-deoxy-3'-[^<18>F]fluorothymidine (^<18>F-FLT), a positron emission tomography (PET) tracer, is taken up by cells and phosphorylated by thymidine kinase 1, which is closely tied to cellular proliferation. The aim of this study was to evaluate ^<18>F-FLT as a tumor proliferation marker. Methods : Four cell lines, SCCVII, PANC-1, LS174T, and HeLa show different growth rate in vivo. Tumor uptake of ^<18>F-FLT was compared to the doubling time of tumor in mice transplanted with these cells. The effect of X-ray irradiation on the uptake of ^<18>F-FLT, ^<18>F-fluoro-2-deoxy-D-glucose (^<18>F-FDG), ^3H-methyl-thymidine (^3H-Thd), ^<14>C-2-deoxy-D-glucose (^<14>C-DG) was examined in tumor-bearing mice between 6 hrs and 7 days after 20 Gy irradiation. Tumor uptake of each radiopharmaceutical was also examined at 24 hours after photodynamic therapy. The uptake of radiopharmaceuticals in tumor was determined at 1 hour after intravenous administration. Results : There was no relation between the doubling time and uptake of ^<18>F-FLT among 4 cell lines. Tumor uptake of ^<18>F-FLT and ^3H-Thd significantly decreased at 6 hours after X-ray irradiation. The uptake of ^<18>F-FDG and ^<14>C-DG, however, did not decrease until 3 days after irradiation. Photodynamic therapy decreased the uptake of ^<18>F-FLT and ^3H-Thd but not the uptake of ^<18>F-FDG nor ^<14>C-DG at 24 hours after therapy. Conclusion : ^<18>F-FLT is more sensitive than ^<18>F-FDG for the evaluation of the response to radiation therapy or photodynamic therapy.