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Monitoring of Herpes Simplex Virus Thymidine Kinase Enzyme Activity Using Positron Emission Tomography¹

Department of Medical Oncology [G. A. P. H., A. C., N. H. M.] and Positron Emission Tomography Center [A. v. W., P. D., W. V., E. F. J. d. V.], Groningen University Hospital, 9700 RB Groningen, the Netherlands

9-[(1-[¹⁸F]Fluoro-3-hydroxy-2-propoxy)methyl]guanine ([¹⁸F]FHPG) was evaluated 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 [¹⁸F]FHPG for 2 h. The in vitro tracer uptake in HSV-tk-containing C6tk cells was 35 ± 5 times higher than that in control cells. In nude rats carrying both a C6 and a C6tk tumor, the average ratio of tracer accumulation between the tumors was 15 ± 5 at 2 h postinjection. The tracer is rapidly cleared from nontarget tissue into the urine because only the HSV-tk-expressing tumor, kidneys, and bladder remained visible on the late PET images. HPLC analysis revealed that three metabolites, tentatively assigned as FHPG mono-, di-, and triphosphate, were formed in the C6tk tumors only. In conclusion, we have demonstrated that [¹⁸F]FHPG is a promising tracer for monitoring HSV-tk enzyme activity in vivo with PET.

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