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

Item Type:	Article
Title:	A sensitive noninvasive method for monitoring successful liver-directed gene transfer of the low-density lipoprotein receptor in Watanabe hyperlipidemic rabbits in vivo
Creators Name:	Tietge, U.J.F. and Cichon, G. and Buettner, C. and Genschel, J. and Heeren, J. and Gielow, P. and Grewe, N. and Dogar, M. and Beisiegel, U. and Manns, M.P. and Lochs, H. and Burchert, W. and Schmidt, H.H.J.
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-density lipoprotein (LDL) receptor (LDLR) transgene expression after adenoviral gene transfer into LDLR-deficient Watanabe hypercholesterolemic rabbits by following tissue uptake of intravenously injected (111)In-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.
Keywords:	Adenovirus, Familial hypercholesterolemia, Indium, Scintillation camera, Kinetics, Animals, Rabbits
Source:	Gene Therapy
ISSN:	0969-7128
Publisher:	Nature Publishing Group
Volume:	11
Number:	7
Page Range:	574-580
Date:	April 2004
Official Publication:	https://doi.org/10.1038/sj.gt.3302206
PubMed:	View item in PubMed

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