A sensitive noninvasive method for monitoring successful liver-directed gene transfer of the low-density lipoprotein receptor in Watanabe hyperlipidemic rabbits in vivo

Abstract

Noninvasive tools to quantitate transgene expression directly are a prerequisite for clinical gene therapy. We established a method to determine location, magnitude, and duration of low-densitiy lipoprotein (LDL) receptor (LDLR) transgene expression after adenoviral gene transfer into LDLR-deficient Watanabe hypercholesterolemic rabbits by following tissue uptake of intravenously injected 111In-labeled LDL using a scintillation camera. Liver-specific tracer uptake was calculated by normalizing the counts measured over the liver to counts measured over the heart that represent the circulating blood pool of the tracer (liver/heart (L/H) ratio). Our results indicate that the optimal time point for transgene imaging is 4 h after the tracer injection. Compared with control virus-injected rabbits, animals treated with the LDLR-expressing adenovirus showed seven-fold higher L/H ratios on day 6 after gene transfer, and had still 4.5-fold higher L/H ratios on day 30. This imaging method might be a useful strategy to obtain reliable data on functional transgene expression in clinical gene therapy trials of familial hypercholesterolemia.

DOI: 10.1038/sj.gt.3302206

Cite this paper

@article{Tietge2004ASN, title={A sensitive noninvasive method for monitoring successful liver-directed gene transfer of the low-density lipoprotein receptor in Watanabe hyperlipidemic rabbits in vivo}, author={U J F Tietge and Guenter Cichon and Christoph Buettner and Janine Genschel and Joerg Heeren and Peter Gielow and Norbert Grewe and M. Zahoor-ul-Hassan Dogar and Ulrike Beisiegel and M. Manns and Herbert Lochs and Wolfgang Burchert and H H-J Schmidt}, journal={Gene Therapy}, year={2004}, volume={11}, pages={574-580} }