title: 8-[18F]Fluoropenciclovir: an improved reporter probe for imaging HSV1-tk reporter gene expression in vivo using PET.
abstract: We have synthesized and evaluated 8-[18F]fluoropenciclovir (FPCV) and compared it with 8-[18F]fluoroganciclovir (FGCV) for monitoring the expression of herpes simplex virus type 1 thymidine kinase (HSV1 -tk) reporter gene in cell culture and in vivo.
  
  
  METHODS
  C6 rat glioma cells stably transfected with HSV1-tk (C6-stb-tk+) and control C6 cells were evaluated for their ability to accumulate FGCV versus FPCV. For in vivo studies, 15 mice were injected by tail vein with increasing levels of an adenoviral vector carrying HSV1-tk. Forty-eight hours later the mice were injected with FPCV and killed 3 h later. The percentage injected dose per gram (%ID/g) liver was then determined. Two additional mice were studied by microPET and autoradiography using FPCV to image adenoviral-mediated hepatic HSV1-tk reporter gene expression. A tumor-bearing mouse (C6 control and C6-stb-tk+) was imaged with FDG, FGCV, and FPCV. Two mice carrying tumors expressing two different reporter genes, HSV1-tk and dopamine type 2 receptor (D2R), were also imaged by microPET using FPCV (day 1) and 3-(2'-[18F]fluoroethyl)spiperone (FESP) (day 2).
  
  
  RESULTS
  FPCV shows a significantly greater accumulation in C6-stb-tk+ cells than does FGCV (P < 0.05). Over identical ranges of adenoviral administration, mouse liver shows a higher %ID/g liver for FPCV (0%-9%) compared with our previously reported results with FGCV (0%-3%). In C6 control and C6-stb-tk+ tumor-bearing mice, FPCV has a greater accumulation than does FGCV for equal levels of HSV1-tk gene expression. In mice carrying tumors expressing either HSV1-tk or D2R reporter genes, there is a corresponding retention of FPCV and FESP, respectively.
  
  
  CONCLUSIONS
  These results indicate that FPCV is a better reporter probe than is FGCV for imaging lower levels of HSV1 -tk gene expression in vivo. The results also reveal the ability to monitor the expression of two distinct reporter genes in the same animal using reporter probes specific for each gene.
authors.affiliation: Crump Institute for Molecular Imaging, UCLA/Department of Energy Laboratory of Structural Biology and Molecular Medicine, UCLA-Jonsson Comprehensive Cancer Center, UCLA School of Medicine, Los Angeles, California 90095-1770, USA.
authors.forename: M
authors.initials: M
authors.lastname: Iyer
authors.forename: J R
authors.initials: JR
authors.lastname: Barrio
authors.forename: M
authors.initials: M
authors.lastname: Namavari
authors.forename: E
authors.initials: E
authors.lastname: Bauer
authors.forename: N
authors.initials: N
authors.lastname: Satyamurthy
authors.forename: K
authors.initials: K
authors.lastname: Nguyen
authors.forename: T
authors.initials: T
authors.lastname: Toyokuni
authors.forename: M E
authors.initials: ME
authors.lastname: Phelps
authors.forename: H R
authors.initials: HR
authors.lastname: Herschman
authors.forename: S S
authors.initials: SS
authors.lastname: Gambhir
mesh_terms: D000212:Acyclovir / Q000031:analogs & derivatives*; D000256:Adenoviridae; D000818:Animals; D000998:Antiviral Agents; D002478:Cells, Cultured; D005462:Fluorine Radioisotopes; D015870:Gene Expression; D017930:Genes, Reporter; D005822:Genetic Vectors; D006147:Guanine; D018259:Herpesvirus 1, Human / Q000201:enzymology / Q000235:genetics*; D051379:Mice; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics*; D014055:Tomography, Emission-Computed
chemical_list: C419962:8-fluoropenciclovir; D000998:Antiviral Agents; D005462:Fluorine Radioisotopes; D017448:Receptors, Dopamine D2; C053539:penciclovir; D006147:Guanine; D013937:Thymidine Kinase; D000212:Acyclovir