Gene Therapy 11 (7): 574-580 (2004-04)

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.; Schmidt H.H.J.

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

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

Type: Article

PubMed: 14724675
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