Small Animal Imaging of Prostate Cancer Therapies

Washington University, Saint Louis MO

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Abstract

DESCRIPTION (provided by applicant): This investigation would explore a hypothesis regarding the relationship in prostate cancer between androgen receptors, anti-androgen therapy, HIF-1 alpha and hypoxia in an animal model of direct relevance to humans. HIF-1 expression has already been shown to be a direct marker of oxygenation in tumors. Direct imaging of this protein would not only provide further insight into prostate cancer biochemistry, but also aid clinicians in designing appropriate treatment schemes. This proposal is aimed at delineating the relationship between androgen ablation therapy, hypoxia, and HIF-1 alpha expression while also monitoring changes in blood flow and metabolism in animal models of prostate cancer. The specific aims, in brief, are (1) To utilize microPET imaging to delineate changes in hypoxia, blood flow, metabolism, androgen receptor expression, cellular proliferation, and HIF-1 alpha expression in animal models of prostate cancer; (2) To conjugate an anti-HIF-1 alpha antibody with DOTA and label with 64Cu; and (3) To correlate immunohistochemical and autoradiographic data of HIF-1 alpha expression with imaging results.