Highly Paramagnetic, Biodegradable Nanoclusters for Imaging Prostate Cancer

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DESCRIPTION (provided by applicant): The widespread use of prostate-specific antigen (PSA) screening has led to earlier detection and a dramatic reduction in overall mortality of prostate cancer; however it has also resulted in over diagnosis and over treatment of indolent disease. PSA-triggered biopsies are generally performed to improve specificity, but biopsies have also proven to be inaccurate in the staging of prostate cancer because of the inherent heterogeneity of most tumors. We hypothesize that molecular imaging strategies offer an opportunity for improved differential diagnoses and staging, due to the ability to provide more accurate information on the location, size, extent, and grade of disease. The overall objective of this proposal is to develop tumor-targeted Gd-conjugated dendrimer nanoclusters (DNCs) as an ultra-sensitive T1 magnetic resonance (MR) imaging contrast agents for the specific detection of prostate cancer. DNCs will be conjugated to the scFv of antibody F77, which recognizes a unique glycolipid antigen that is specifically expressed on the cell surface of both androgen-dependent and androgen-independent prostate cancer cells. The specific aims for the proposal are (1) to synthesize biodegradable, Gd-conjugated DNCs; (2) evaluate the toxicity, specific targeting capabilities, and uptake of tumor-targeted DNCS in culture; and (3) evaluate the ability to detect tumors in orthotopic mouse models of prostate cancer. The long-term goal of this proposal is to develop a contrast agent that can provide improved differential diagnoses and staging of prostate cancer and thus reduce or eliminate the over-treatment of the disease.