Imaging adenoviral-directed reporter gene expression in living animals with positron emission tomography.
We are developing quantitative assays to repeatedly and noninvasively image expression of reporter genes in living animals, using positron emission tomography (PET). We synthesized positron-emitting 8-[18F]fluoroganciclovir (FGCV) and demonstrated that this compound is a substrate for the herpes simplex virus 1 thymidine kinase enzyme (HSV1-TK). Using positron-emitting FGCV as a PET reporter probe, we imaged adenovirus-directed hepatic expression of the HSV1-tk reporter gene in living mice. There is a significant positive correlation between the percent injected dose of FGCV retained per gram of liver and the levels of hepatic HSV1-tk reporter gene expression (r2 > 0.80). Over a similar range of HSV1-tk expression in vivo, the percent injected dose retained per gram of liver was 0-23% for ganciclovir and 0-3% for FGCV. Repeated, noninvasive, and quantitative imaging of PET reporter gene expression should be a valuable tool for studies of human gene therapy, of organ/cell transplantation, and of both environmental and behavioral modulation of gene expression in transgenic mice.
The Crump Institute for Biological Imaging, University of California School of Medicine, Los Angeles, CA 90095-1770, USA.
S S
SS
Gambhir
J R
JR
Barrio
M E
ME
Phelps
M
M
Iyer
M
M
Namavari
N
N
Satyamurthy
L
L
Wu
L A
LA
Green
E
E
Bauer
D C
DC
MacLaren
K
K
Nguyen
A J
AJ
Berk
S R
SR
Cherry
H R
HR
Herschman
D000818:Animals; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D015774:Ganciclovir / Q000493:pharmacokinetics*; D017930:Genes, Reporter; D015316:Genetic Therapy / Q000379:methods; D005910:Glioma; D018259:Herpesvirus 1, Human / Q000235:genetics*; D006801:Humans; D008099:Liver / Q000000981:diagnostic imaging*; D051379:Mice; D008822:Mice, Transgenic; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis; D013937:Thymidine Kinase / Q000096:biosynthesis / Q000235:genetics*; D014055:Tomography, Emission-Computed / Q000379:methods; D014158:Transcription, Genetic; D014162:Transfection; D014316:Tritium / Q000493:pharmacokinetics; D014407:Tumor Cells, Cultured
D019275:Radiopharmaceuticals; D011994:Recombinant Proteins; D019788:Fluorodeoxyglucose F18; D014316:Tritium; D013937:Thymidine Kinase; D015774:Ganciclovir