Evaluation of N3-18F-FPrT, 18F-FLT and 18F-FMAU as PET probes in a tumor-bearing animal model

Objectives This study compared the effectiveness of three 18F-labeled thymidine analogues, N3-(3-18F-fluoropropyl)-thymidine (N3-18F-FPrT), 18F-FLT and 18F-FMAU, for the tumor detection with small animal PET in a NG4TL4 sarcoma-bearing mouse model.

Methods Starting from 3’,5’-Di-O-toluoyl-N3-(3-bromopropyl)-thymidine, N3-18F-FPrT was prepared in 1.5 h with acceptable radiochemical yield (30%, decay corrected) and high radiochemical purity (≧98%). 18F-FLT and 18F-FMAU were prepared according to the literature. Biological characterizations were performed to evaluate their potential for tumor detection.

Results The uptake of N3-18F-FPrT in NG4TL4 cell culture reached the plateau (cell-to-medium ratio, C/M, 2.71±0.027) after 10 min incubation, while that of 18F-FLT and 18F-FMAU kept increasing with time (C/M of 78.67±7.82 and 12.53±3.04 after 2 h incubation, respectively). Dynamic small animal PET imaging of tumor-bearing mice after administration of these three tracers all revealed rapid and significant tumor uptakes. Higher tumor-to-muscle ratios (T/M) derived from the images after administration of 18F-FLT (2.25±0.263 at 1 h p.i.) and 18F-FMAU (2.17±0.19 at 1 h p.i.) compared with that of N3-18F-FPrT (1.40±0.11 at 1 h p.i.) evidenced the more specific retention of these two tracers in tumor. The results of tracer biodistribution studies in tumor-bearing animals were consistent with those observed in imaging.

Conclusions 18F-FLT is demonstrated most promising (highest C/M ratio and T/M ratio) among these three PET probes for tumor detection by cellular uptake and animal studies, while N3-18F-FPrT only shows limited potential as a proliferation probe