[(11)C]FMAU and [(18)F]FHPG as PET tracers for herpes simplex virus thymidine kinase enzyme activity and human cytomegalovirus infections.
[(11)C]-2'-Fluoro-5-methyl-1-beta-D-arabinofuranosyluracil ([(11)C]FMAU) and [(18)F]-9-[(3-fluoro-1-hydroxy-2-propoxy)methyl]guanine ([(18)F]FHPG), radiolabeled representatives of two classes of antiviral agents, were evaluated as tracers for measuring herpes simplex virus thymidine kinase (HSV-tk) enzyme activity after gene transfer and as tracers for localization of active human cytomegalovirus (HCMV) infections. In vitro accumulation experiments revealed that both [(11)C]FMAU and [(18)F]FHPG accumulated significantly more in HSV-tk expressing cells than they did in control cells. [(18)F]FHPG uptake 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 transport or cell type dependent substrate specific susceptibility of the enzyme. In vitro, both tracers exhibited a good selectivity for accumulation in HCMV-infected human umbilical vein endothelial cells over uninfected cells. In contrast to [(18)F]FHPG, [(11)C]FMAU uptake in control cells was relatively high due to phosphorylation of the tracer by host kinases. Therefore, [(18)F]FHPG appears to be the more selective tracer not only to predict HSV-tk gene therapy outcome, but also to localize active HCMV infections with PET.
de Vries
E F
EF
PET Center, Groningen University Hospital, Groningen, The Netherlands. e.f.j.de.vries@pet.azg.nl
van Waarde
A
A
Harmsen
M C
MC
Mulder
N H
NH
Vaalburg
W
W
Hospers
G A
GA
D000998:Antiviral Agents / Q000494:pharmacology; D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives*; D002460:Cell Line; D003586:Cytomegalovirus Infections / Q000000981:diagnostic imaging* / Q000201:enzymology; D015774:Ganciclovir / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D019275:Radiopharmaceuticals; D018139:Simplexvirus / Q000201:enzymology*; D013937:Thymidine Kinase / Q000378:metabolism*; D014055:Tomography, Emission-Computed
C104325:9-((3-fluoro-1-hydroxy-2-propoxy)methyl)guanine; D000998:Antiviral Agents; D019275:Radiopharmaceuticals; D001086:Arabinofuranosyluracil; D017853:Phosphotransferases (Alcohol Group Acceptor); C075365:ganciclovir kinase; D013937:Thymidine Kinase; C034935:clevudine; D015774:Ganciclovir