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

目的：3‘-脱氧-3’-氟代胸苷(F-F)是一种正电子发射断层扫描(PET)示踪剂，被细胞摄取并被胸苷激酶1磷酸化，与细胞增殖密切相关。本研究的目的是评价F-Flt作为肿瘤增殖标记物的作用。方法：四种细胞株SCCVII、PANC-1、LS174T和HeLa在体内表现出不同的生长速度。将移植了这些细胞的小鼠的肿瘤摄取与肿瘤倍增时间进行了比较。本文观察了X射线照射对荷瘤小鼠照射后6小时至7天摄取~(18)F-氟-2-脱氧-D-葡萄糖(~&lt；18&gt；F-FDG)、~3H-甲基-胸腺嘧啶核苷(~3H-THD)、~(14&gt)C-2-脱氧-D-葡萄糖(~(14&lt；14&gt；C-DG))的影响。在光动力治疗后24小时还检测了肿瘤对每种放射性药物的摄取情况。静脉给药后1h测定肿瘤对放射性药物的摄取。结果：4种细胞系的倍增时间与摄取~(18)&GT；F-Flt无相关性。照射后6h，肿瘤对~(18)F-Flt和~(3 H)-THD的摄取显著降低。然而，~(18)F-FDG和~(14)C-DG的摄取直到照射后3天才开始下降。在治疗后24小时，光动力疗法可减少~(18)&gt；F-flt；~(3 H)-THD的摄取，但不减少~(18)&gt；F-FDG或~(14)&gt；C-dG的摄取。结论：在评价放射治疗或光动力治疗的疗效方面，18F-Flt比18F-FDG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.