[C-11]FMAU and [F-18]FHPG as PET tracers for herpes simplex virus thymidine kinase enzyme activity and human cytomegalovirus infections

[C-11]-2'-Fluoro-5-methyl-1-beta-D-arabinofuranosyluracil ([C-11]FMAU) and [F-18]-9-[(3-fluoro-1-hydroxy-2-propoxy)methyl]guanine ([F-18]FHPG), radiol abeled representatives of two classes of antiviral agents, were evaluated a s tracers for measuring herpes simplex virus thymidine kinase (HSV-tk) enzy me activity after gene transfer and as tracers for localization of active h uman cytomegalovirus (HCMV) infections. In vitro accumulation experiments r evealed that both [C-11]FMAU and [F-18]FHPG accumulated significantly more in HSV-tk expressing cells than they did in control cells. [F-18]FHPG uptak e in HSV-tk expressing cells, however, was found to depend strongly on the cell line used, which might be due to cell type dependent membrane transpor t or cell type dependent substrate specific susceptibility of the enzyme. I n vitro, both tracers exhibited a good selectivity for accumulation in HCMV -infected human umbilical vein endothelial cells over uninfected cells. In contrast to [F-18]FHPG, [C-11]FMAU uptake in control cells was relatively h igh due to phosphorylation of the tracer by host kinases. Therefore, [F-18] FHPG appears to be the more selective tracer not only to predict HSV-tk gen e therapy outcome, but also to localize active HCMV infections with PET. NU CL MED BIOL 27;2:113-119, 2000. (C) 2000 Elsevier Science Inc. All rights r eserved.