Evaluation of 2′-Deoxy-2′-flouro-5-methyl-1-β-d-arabinofuranosyluracil as a potential gene imaging agent for HSV-tk expression in vivo

2′-Deoxy-2′-flouro-5-methyl-1-β-D-arabinofuranosyluracil (FMAU) has been evaluated in HT-29 cells as a potential positron emission tomography (PET) radiotracer for imaging HSV-tk gene expression in vivo. In vitro experiments demonstrate that the accumulation of [¹⁴C]-FMAU in HSV-tk-expressing cells is 2.4-fold (p < .02), 4.0-fold (p < .001), and 5.3-fold (p < .001) higher than the wild-type cells at 1, 3, and 5 hr, respectively. In vivo studies revealed that the tumor uptake in HSV-tk-expressing cells was 2.3-fold (p < .001), 3.0-fold (p < .001), and 5.5-fold (p < .001) higher than the control cells at 1,2, and 5 hr, respectively. FMAU was found to be more sensitive compared to our earlier studies using 9-[(3-¹⁸F-fluoro-1-hydroxy-2-propoxy)methyl]-guanine ([¹⁸F]-FHPG) and 9-(4[ ¹⁸F]-fluoro-3-hydroxy-methylbutyl)guanine ([¹⁸F]-FHBG) in the same cell lines, although, the specificity was less than FHBG. These results suggest that while FMAU labeled with PET isotopes may be useful for imaging HSV-tk-expressing tumors in vivo, multitracer studies across additional tumor models are necessary in order to identify an optimal PET radiotracer.