Our long-range objectives are to develop PET imaging techniques for brain tumor imaging in order to identify molecular structures and receptors that are altered during brain tumor growth and spread and to help predict the natural history and response to therapy. The objective in this proposal is to image brain tumor angiogenesis and anti-angiogenic therapy efficacy by means of PET and MRI. Brain tumors are angiogenesis dependent. Anti-angiogenic therapies that either block expression of tumor angiogenesis related proteins or directly prevent endothelial cells from migration and induce apoptosis, have been proven effective in brain tumors. We have previously developed a series of cyclic RGB peptide radiotracers for PET imaging of brain tumor models based upon av-integrin antagonism. The tumor targeting efficacy and pharmacokinetics of the tracers are highly dependent on their receptor binding affinity, hydrophilicity, and molecular size, etc. This project will expand our investigations with aim to: (1) optimize the integrin specific PET tracers for clinical applicability; (2) correlate alpha-v integrin expression level with the magnitude of tumor (both tumor cells and rumor vasculature) tracer uptake; and (3) evaluate anti-integrin brain tumor treatment with a PET/MRI combination. Overall, this proposal will foster in a novel and unique way our understanding of brain tumor angiogenesis in relationship to alpha-v integrin expression and allow for direct assessment of anti-angiogenic treatment efficacy based upon alpha-integrin targeted PET imaging. This should lead to direct clinical translation of the PET probes validated and also allow imaging of angiogensis for other tumors (e.g., for lymphomas studied in Research Project 2). Furthermore it should help show the role of imaging to monitor anti-cancer therapies for acceleration of testing of new generation of anti-angiogenesis agents.
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