Evaluation of 2'-deoxy-2'-[18F]fluoro-5-methyl-1-beta-L: -arabinofuranosyluracil ([18F]-L: -FMAU) as a PET imaging agent for cellular proliferation: comparison with [18F]-D: -FMAU and [18F]FLT.
OBJECTIVE
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.
Nishii
Ryuichi
R
Department of Experimental Diagnostic Imaging, M. D. Anderson Cancer Center, The University of Texas, Box 059, T8.3895, 1515 Holcombe Blvd, Houston, TX 77030, USA.
Volgin
Andrei Y
AY
Mawlawi
Osama
O
Mukhopadhyay
Uday
U
Pal
Ashutosh
A
Bornmann
William
W
Gelovani
Juri G
JG
Alauddin
Mian M
MM
D000818:Animals; D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives*; D049109:Cell Proliferation; D015224:Dideoxynucleosides; D005462:Fluorine Radioisotopes; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D015224:Dideoxynucleosides; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D001086:Arabinofuranosyluracil; C034935:clevudine; C002854:alovudine