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

Gene Therapy volume 11, pages 574–580 (2004)Cite this article

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.

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Acknowledgements

We are indebted to Sigrid Ohlendorf and Regina Haas for excellent technical assistance. This work was supported by a grant from the Bundesministerium für Bildung und Forschung (FKZ: 01KV9549/4 and 01KV9904).

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Authors and Affiliations

  1. Department of Medicine and NWFZ, Charité Campus Mitte, Humboldt University, Berlin, Germany

    UJF Tietge

  2. Department of Molecular Cell Biology, Institute for Biology, Humboldt University Berlin at the Max-Delbrueck-Center for Molecular Medicine, Berlin, Germany

    G Cichon & H Lochs

  3. Clinic of Gastroenterology, Hepatology, and Endocrinology, Charité Campus Mitte, Humboldt University, Berlin, Germany

    C Büttner, J Genschel & HH-J Schmidt

  4. Institute of Molecular Cell Biology, Center for Experimental Medicine, University Hospital Eppendorf, Hamburg, Germany

    J Heeren & U Beisiegel

  5. Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany

    P Gielow

  6. Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany

    N Grewe, M Dogar & MP Manns

  7. Institute of Molecular Biophysics, Radiopharmacy and Nuclear Medicine, Heart and Diabetes Center North Rhine-Westphalia, Bad Oeynhausen, Germany

    W Burchert

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  1. UJF Tietge
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Tietge, U., Cichon, G., Büttner, C. et al. A sensitive noninvasive method for monitoring successful liver-directed gene transfer of the low-density lipoprotein receptor in Watanabe hyperlipidemic rabbits in vivo. Gene Ther 11, 574–580 (2004). https://doi.org/10.1038/sj.gt.3302206

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  • DOI: https://doi.org/10.1038/sj.gt.3302206

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