In this proposal we will explore application of noninvasive MR imaging to study incorporation of bone- marrow-derived endothelial precursor cells to the neovasculature of prostate cancer models. After initial response to hormonal therapy most prostate cancers resume growth and eventually progress to malignant disease. To control the androgen-independent disease at this stage novel efficient treatments are required. Antiangiogenic therapy is an important new form of cancer chemotherapy that was shown to be effective against prostate cancer when used alone or in combination with traditional cytotoxic chemotherapy. Design of successful and efficient antiangiogenic therapy requires a clear understanding of the complex process of tumor vascularization and role of various components of angiogenesis. In this project we propose to use noninvasive MR imaging to study an alternative mechanism of tumor vasculature formation that relies on the recruitment of vascular progenitor cells to tumor neovasculature. Circulating bone-marrow derived cells are attracted to growing tumors, divide, and differentiate to reduce new endothelial cells. Therefore these progenitor cells can be an important component of the tumor angiogenesis and can also be a target for novel forms of antiangiogenic therapy. We propose to develop a novel MR imaging method for direct visualization of vascular progenitor cells using specific contrast agents targeted to engineered cell-surface receptors expressed on the plasma membrane of the progenitor cells. This method will allow a long-term monitoring of the progenitor cells in tumors in vivo using noninvasive MR imaging. We will monitor incorporation of these cells to the vasculature of growing prostate cancers in animal models. We will also follow the effect of different forms of antiangiogenic therapy on the process of progenitor cell recruitment and incorporation to the tumor vasculature. ? ? ?
