Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2333-2338 |
| Number of pages | 6 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 96 |
| Issue number | 5 |
| DOIs | |
| State | Published - Mar 2 1999 |
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ASJC Scopus subject areas
- Genetics
- General
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Imaging adenoviral-directed reporter gene expression in living animals with positron emission tomography. / Gambhir, Sanjiv S.; Barrio, Jorge R.; Phelps, Michael E.; Iyer, Meera; Namavari, Mohammad; Satyamurthy, Nagichettiar; Wu, Lily; Green, Leeta A.; Bauer, Eileen; Maclaren, Duncan C.; Nguyen, Khoi; Berk, Arnold J.; Cherry, Simon R; Herschman, Harvey R.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 96, No. 5, 02.03.1999, p. 2333-2338.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Imaging adenoviral-directed reporter gene expression in living animals with positron emission tomography
AU - Gambhir, Sanjiv S.
AU - Barrio, Jorge R.
AU - Phelps, Michael E.
AU - Iyer, Meera
AU - Namavari, Mohammad
AU - Satyamurthy, Nagichettiar
AU - Wu, Lily
AU - Green, Leeta A.
AU - Bauer, Eileen
AU - Maclaren, Duncan C.
AU - Nguyen, Khoi
AU - Berk, Arnold J.
AU - Cherry, Simon R
AU - Herschman, Harvey R.
PY - 1999/3/2
Y1 - 1999/3/2
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=13044260220&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=13044260220&partnerID=8YFLogxK
U2 - 10.1073/pnas.96.5.2333
DO - 10.1073/pnas.96.5.2333
M3 - Article
VL - 96
SP - 2333
EP - 2338
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 5
ER -