Quantitative imaging of Na/I symporter transgene expression using positron emission tomography in the living animal

Thomas Groot-Wassink, Eric O. Aboagye, Yaohe Wang, Nicholas R. Lemoine, Andrew J. Reader, Georges Vassaux

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Transgene expression can be measured in living animals by positron emission tomography (PET) using reporter genes associated with radiolabeled substrates or ligands. We examined here whether PET images obtained with a new reporter gene system (sodium/iodide symporter (NIS) and [124I]iodide) could provide quantitative information on gene expression in mice. Mice received various doses of recombinant adenovirus in which the expression of the NIS cDNA was driven by the CMV promoter and subsequently [124I]iodide. Postmortem γ counting of liver biopsies was correlated to the adenovirus dose and with NIS mRNA concentration. In addition, immunohistochemically NIS-positive cells increased with higher tissue activities. Finally, a linear relationship existed between the postmortem γ counting in liver tissues and that calculated from images obtained through small animal PET scanning (r = 0.9581), although there was a bias at high and low specific values. This systematic study on 35 animals demonstrates that quantitative information on gene expression can be obtained from PET images using the NIS reporter system. This new methodology of quantitative imaging of gene expression presents the advantage of avoiding extensive radiochemistry, an important step for more disseminated use of this emerging technology. In addition, this work supports further development of the NIS system for noninvasive assessment of gene delivery in preclinical and clinical studies. Copyright © The American Society of Gene Therapy.
    Original languageEnglish
    Pages (from-to)436-442
    Number of pages6
    JournalMolecular Therapy
    Volume9
    Issue number3
    DOIs
    Publication statusPublished - Mar 2004

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