Direct Comparison of Radiolabeled Probes FMAU, FHBG, and FHPG as PET Imaging Agents for HSV1-tk Expression in a Human Breast Cancer Model

2'-Deoxy-2'-fluoro-5-methyl-1-beta-D-arabinofuranosyluracil (FMAU), 9-(4-fluoro-3-hydroxy-methyl-butyl)guanine (FHBG) and 9-[(3-fluoro-1-hydroxy-2-propoxy)methyl]-guanine (FHPG) have been evaluated in a human breast cancer model as potential radiotracers for PET imaging of HSV1-tk gene expression. In vitro accumulation of [C-14] FMAU, [F-18] FHBG, and [F-18] FHPG in HSV1-tk-expressing cells was 14- to 16-fold (p < .001), 9- to 13-fold (p < .001), and 2- to 3-fold (p < .05) higher than tk-negative control cells, respectively, between 30 and 240 min. Accumulation of FMAU and FHBG in vector-transduced cells was 10- to 14-fold and 6- to 10-fold higher than wild-type cells, respectively. At 2 hr, uptake of [C-14] FMAU in tk-positive cells was 6.3-fold and 60-fold higher than [F-18] FHBG and [F-18] FHPG, respectively. In vivo, tumor uptake of [C-14] FMAU in HSV1-tk-expressing cells was 3.7-fold and 5.5-fold (p < .001) higher than tk-negative control cells at 1 and 2 hr, respectively. Tumor uptake of [F-18] FHBG was 4.2-fold and 12.6-fold higher (p < .001) than tk-negative cells at the same time points. Incorporation of [C-14] FMAU in tk-positive tumor was 18-fold and 24-fold higher (p < .001) than [F-18] FHBG at 1 and 2 hr, respectively. Micro-PET images support the biodistribution results and indicate that both [F-18] FMAU and [F-18] FHBG are useful for imaging HSV1-tk expression in breast cancer. Although FMAU demonstrates higher total incorporation (%dose/g) in tumor tissue compared with the other tracers, FHBG is superior in terms of specific accumulation in transfected cells at later time points. Mol Imaging (2004) 3, 76-84.