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 journalArticle

16 Scopus citations

Abstract

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
Volume62
Issue number2
DOIs
StatePublished - Aug 1 2009

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Keywords

  • DCE-MRI
  • EPRI
  • Gene therapy
  • Hypoxia

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Haney, C. R., Parasca, A. D., Fan, X., Bell, R. M., Zamora, M. A., Karczmar, G. S., Mauceri, H. J., Halpern, H. J., Weichselbaum, R. R., & Pelizzari, C. A. (2009). Characterization of response to radiation mediated gene therapy by means of multimodality imaging. Magnetic resonance in medicine, 62(2), 348-356. https://doi.org/10.1002/mrm.22008