Characterization of response to radiation mediated gene therapy by means of multimodality imaging

Chad R. Haney, Adrian D. Parasca, Xiaobing Fan, Rebecca M. Bell, Marta A. Zamora, Gregory S. Karczmar, Helena J. Mauceri, Howard J. Halpern, Ralph R. Weichselbaum, Charles A. Pelizzari

    Research output: Contribution to journalArticlepeer-review

    16 Scopus citations


    Imaging techniques are under development to facilitate early analysis of spatial patterns of tumor response to combined radiation and antivascular gene therapy. A genetically modified, replication defective adenoviral vector (Ad.EGR-TNFα), injected intratumorally, mediates infected cells to express tumor necrosis factor alpha (TNFα), which is increased after exposure to radiation. The goal of this study was to characterize an image based "signature" for response to this combined radiation and gene therapy in mice with human prostate xenografts. This study is part of an imaged guided therapy project where such a signature would be useful in guiding subsequent treatments. Changes in the tumor micro-environment were assessed using MRI registered with electron paramagnetic resonance imaging which provides images of tissue oxygenation. Dynamic contrast-enhanced MRI was used to assess tissue perfusion. When compared with null vector (control) treatment, the ratio of contrast agent (Gd-DTPA-BMA) washout rate to uptake rate was lower (P = 0.001) after treatment, suggesting a more balanced perfusion. Concomitantly, oxygenation significantly increased in the treated animals and decreased or did not change in the control animals (P < 0.025). This is the first report of minimally invasive, quantitative, absolute oxygen measurements correlated with tissue perfusion in vivo.

    Original languageEnglish (US)
    Pages (from-to)348-356
    Number of pages9
    JournalMagnetic resonance in medicine
    Issue number2
    StatePublished - Aug 2009


    • DCE-MRI
    • EPRI
    • Gene therapy
    • Hypoxia

    ASJC Scopus subject areas

    • Radiology Nuclear Medicine and imaging


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