Monitoring of herpes simplex virus thymidine kinase enzyme activity using positron emission tomography

9-[(1-[F-18]Fluoro-3-hydroxy-2-propoxy)methyl]guanine ([F-18]FHPG) wasevalu ated as a tracer for noninvasive positron emission tomography (PET) imaging of herpes simplex virus type 1 thymidine kinase (HSV-tk) gene expression. C6 rat glioma cells with and without the HSV-tk gene were incubated with [F -18]FHPG for 2 h. The in vitro tracer uptake in HSV-tk-containing C6tk cell s wits 35 +/- 5 times higher than that in control cells. In nude rats carry ing both a C6 and a C6tk tumor, the average ratio of tracer accumulation be tween the tumors was 15 +/- 5 at 2 h postinjection. The tracer is rapidly c leared from nontarget tissue into the urine because only the HSV-tk-express ing tumor, kidneys, and bladder remained visible on the late PET images. HP LC analysis revealed that three metabolites, tentatively assigned as FHPG m ono-, di-, and triphosphate, were formed in the C6tk tumors only. In conclu sion, we have demonstrated that [F-18]FHPG is a promising tracer for monito ring HSV-tk enzyme activity in vivo with PET.