Abstract
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.
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Acknowledgments
This work was supported by startup funds from The University of Texas M. D. Anderson Cancer Center to Drs. Mian Alauddin and Juri Gelovani.
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Nishii, R., Volgin, A.Y., Mawlawi, O. et al. 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. Eur J Nucl Med Mol Imaging 35, 990–998 (2008). https://doi.org/10.1007/s00259-007-0649-1
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DOI: https://doi.org/10.1007/s00259-007-0649-1