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

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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.