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

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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., Cichon, G., Buettner, C., Genschel, J., Heeren, J., Gielow, P., Grewe, N., Dogar, M., Beisiegel, U., Manns, M.P., Lochs, H., 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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