Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Republic of Korea.
Anticancer Res. 2014 Feb;34(2):759-66.
We aimed to investigate whether 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT) positron emission tomography (PET) can estimate thymidine kinase 1 (TK1) activity after thymidylate synthase (TS) inhibition by 5-fluorouracil (5-FU) in a mouse tumor model.
Nude mice with HT29 tumors were injected with phosphate-buffered saline or 5-FU (16.7 or 50 mg/kg). Twenty-four hours later, 2-hour dynamic images were acquired after injection of [(18)F]FLT. In another group of mice with HT29 cells, static PET images were obtained 110 min after [(18)F]FLT injection.
Kinetic parameters related to [(18)F]FLT retention increased significantly, whereas the de-phosphorylation of [(18)F]FLT monophosphate decreased significantly. The standardized uptake value (SUVmean) of HT29 tumors correlated significantly with the net influx constant and the distribution volume for phosphorylated [(18)F]FLT. There was a significant correlation between the tumor SUVmean and TK1 activity.
SUVmean at 110-120 min after [(18)F]FLT, can quantitatively evaluate kinetic parameters and TK1 activity after TS inhibition.
我们旨在研究氟代胸苷（[（18）F]FLT）正电子发射断层扫描（PET）是否可以在小鼠肿瘤模型中通过 5-氟尿嘧啶（5-FU）抑制胸苷酸合成酶（TS）后估计胸苷激酶 1（TK1）的活性。
将携带 HT29 肿瘤的裸鼠注射磷酸盐缓冲盐水或 5-FU（16.7 或 50mg/kg）。24 小时后，在注射[（18）F]FLT 后进行 2 小时动态图像采集。在另一组携带 HT29 细胞的小鼠中，在注射[（18）F]FLT 110 分钟后获得静态 PET 图像。
与[（18）F]FLT 保留相关的动力学参数显著增加，而[（18）F]FLT 单磷酸的去磷酸化显著降低。HT29 肿瘤的标准化摄取值（SUVmean）与磷酸化[（18）F]FLT 的净流入常数和分布容积显著相关。肿瘤 SUVmean 与 TK1 活性之间存在显著相关性。
[（18）F]FLT 后 110-120 分钟的 SUVmean，可以定量评估 TS 抑制后动力学参数和 TK1 活性。
