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 to mography (PET). We synthesized positron-emitting 8-[18F]fluoroganciclovir ( FGCV) and demonstrated that this compound is a substrate for the herpes sim plex virus 1 thymidine kinase enzyme (HSV1-TK). Using positron-emitting FGC V as a PET reporter probe, we imaged adenovirus-directed hepatic expression of the HSV1-tk reporter gene in living mice. There is a significant positi ve correlation between the percent injected dose of FGCV retained per gram of liver and the levels of hepatic HSV1-tk reporter gene expression (r(2) > 0.80). Over a similar range of HSV1-tk expression in vivo, the percent inj ected dose retained per gram of liver was 0-23% for ganciclovir and 0-3% fo r FGCV. Repeated, noninvasive, and quantitative imaging of PET reporter gen e expression should be a valuable tool for studies of human gene therapy, o f organ/cell transplantation, and of both environmental and behavioral modu lation of gene expression in transgenic mice.