Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32CA110422-03
Application #
7095900
Study Section
Diagnostic Radiology Study Section (RNM)
Program Officer
Lohrey, Nancy
Project Start
2004-07-01
Project End
2007-06-30
Budget Start
2006-07-01
Budget End
2007-06-30
Support Year
3
Fiscal Year
2006
Total Cost
$48,796
Indirect Cost

  Institution

Name
Washington University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130

  Publications

V?vere, Amy L; Biddlecombe, Gráinne B; Spees, William M et al. (2009) A novel technology for the imaging of acidic prostate tumors by positron emission tomography. Cancer Res 69:4510-6
Vavere, Amy L; Lewis, Jason S (2008) Examining the relationship between Cu-ATSM hypoxia selectivity and fatty acid synthase expression in human prostate cancer cell lines. Nucl Med Biol 35:273-9
Vavere, Amy L; Kridel, Steven J; Wheeler, Frances B et al. (2008) 1-11C-acetate as a PET radiopharmaceutical for imaging fatty acid synthase expression in prostate cancer. J Nucl Med 49:327-34
Bonnitcha, Paul D; Vavere, Amy L; Lewis, Jason S et al. (2008) In vitro and in vivo evaluation of bifunctional bisthiosemicarbazone 64Cu-complexes for the positron emission tomography imaging of hypoxia. J Med Chem 51:2985-91
Vavere, Amy L; Lewis, Jason S (2007) Cu-ATSM: a radiopharmaceutical for the PET imaging of hypoxia. Dalton Trans :4893-902