Monitoring tumor proliferative response to radiotherapy using (18)F-fluorothymidine in human head and neck cancer xenograft in comparison with Ki-67. 
Although radiotherapy is an important treatment strategy for head and neck cancers, it induces tumor repopulation which adversely affects therapeutic outcome.  In this regard, fractionated radiotherapy is widely applied to prevent tumor repopulation.  Evaluation of tumor proliferative activity using (18)F-fluorothymidine (FLT), a noninvasive marker of tumor proliferation, may be useful for determining the optimal timing of and dose in the repetitive irradiation.  Thus, to assess the potentials of FLT, we evaluated the sequential changes in intratumoral proliferative activity in head and neck cancer xenografts (FaDu) using FLT.  FaDu tumor xenografts were established in nude mice and assigned to control and two radiation-treated groups (10 and 20 Gy).  Tumor volume was measured daily. ( 3)H-FLT was injected intravenously 2 h before killing.  Mice were killed 6, 24, 48 h, and 7 days after the radiation treatment.  Intratumoral (3)H-FLT level was visually and quantitatively assessed by autoradiography.  Ki-67 immunohistochemistry (IHC) was performed.  In radiation-treated mice, the tumor growth was significantly suppressed compared with the control group, but the tumor volume in these mice gradually increased with time.  In the visual assessment, intratumoral (3)H-FLT level diffusely decreased 6 h after the radiation treatment and then gradually increased with time, whereas no apparent changes were observed in Ki-67 IHC.  Six hours after the radiation treatment at 10 and 20 Gy, the intratumoral (3)H-FLT level markedly decreased to 45 and 40 % of the control, respectively (P < 0.0001 vs control), and then gradually increased with time.  In each radiation-treated group, the (3)H-FLT levels at 48 h and on day 7 were significantly higher than that at 6 h. The intratumoral (3)H-FLT levels in both treated groups were 68 and 60 % at 24 h (P < 0.001), 71 and 77 % at 48 h (P < 0.001), and 83 and 81 % on day 7 (P = NS) compared with the control group.  Intratumoral FLT uptake level markedly decreased at 6 h and then gradually increased with time.  Sequential evaluation of intratumoral proliferative activity using FLT can be beneficial for determining the optimal timing of and dose in repetitive irradiation of head and neck cancer.