Monitoring of herpes simplex virus thymidine kinase enzyme activity using positron emission tomography.
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.
Hospers
G A
GA
Department of Medical Oncology, Groningen University Hospital, The Netherlands. g.a.p.hospers@int.azg.nl
Calogero
A
A
van Waarde
A
A
Doze
P
P
Vaalburg
W
W
Mulder
N H
NH
de Vries
E F
EF
D000818:Animals; D005260:Female; D005462:Fluorine Radioisotopes; D015774:Ganciclovir / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D020128:Inhibitory Concentration 50; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011923:Rats, Nude; D018139:Simplexvirus / Q000201:enzymology; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism*; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
C104325:9-((3-fluoro-1-hydroxy-2-propoxy)methyl)guanine; D005462:Fluorine Radioisotopes; D013937:Thymidine Kinase; D015774:Ganciclovir