Evaluation of 2′-deoxy-2′-[¹⁸F]fluoro-5-methyl-1- β-l-arabinofuranosyluracil ([¹⁸F]-l-FMAU) as a PET imaging agent for cellular proliferation: Comparison with [¹⁸F]-d-FMAU and [ ¹⁸F]FLT

Purpose: Clevudine (l-FMAU) an un-natural analogue of thymidine, is in clinical trials for the treatment of hepatitis B virus (HBV). l-FMAU is phosphorylated by cellular kinases such as thymidine kinase 1 and deoxycytidine kinase, and its triphosphate form inhibits HBV deoxyribonucleic acid synthesis. Thus, l-FMAU, radiolabeled with an appropriate isotope, may be useful for positron emission tomography (PET) imaging of tumor proliferation. We evaluated [¹⁸F]-l-FMAU as a PET imaging agent in tumor-bearing mice and compared the results with those of two other radiotracers, [¹⁸F]-d- FMAU and [¹⁸F]-FLT. Methods: Subcutaneous xenografts of the human lung cancer cell lines H441 and H3255 were established in mice. A micro-PET scanner was used to obtain images of the tumor-bearing animals with [ ¹⁸F]-l-FMAU, [¹⁸F]-d-FMAU, and [¹⁸F]-FLT. Results: At 2 h postinjection, the tumor uptake (% ID/g) of [ ¹⁸F]-l-FMAU, [¹⁸F]-d-FMAU, and [¹⁸F]-FLT in the faster-growing H441 cells was 3.13±1.11, 7.74±1.39, and 5.10±1.45, respectively. The corresponding values for the slower-growing H3255 cells were 1.38±0.81, 4.49±1.08, and 0.57±0.33. Tumor/muscle ratios of accumulation for [¹⁸F]-l-FMAU, [ ¹⁸F]-d-FMAU, and [¹⁸F]-FLT in H441 cells were 4.15±1.82, 3.37±1.19, and 12.94±4.38, respectively, and the corresponding values in H3255 cells were 1.62±0.50, 1.96±0.74, and 1.50±0.90. Conclusions: [¹⁸F]-l-FMAU may be a useful agent for imaging tumor proliferation in fast-growing human lung cancers by PET.