Radiometal-cyclized Octreotide Derivatives for Oncology

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DESCRIPTION (provided by applicant): Radiolabeled somatostatin analogues are being developed as cancer imaging and radiotherapy agents to target somatostatin receptor-positive tumors. The overall goal of this proposal is to synthesize, characterize and evaluate Tc-99m- and Re-188-cyclized somatostatin peptide derivatives for diagnostic imaging and targeted radiotherapy, respectively, of cancer. The hypothesis to be addressed is that structural modification of somatostatin analogues to increase retention of radioactivity in tumors will result in both improved tumor imaging contrast and more effective therapy at lower doses that would spare the non-target tissues. The objectives of this proposal, in brief, are (1) to synthesize and characterize somatostatin receptor-targeting peptides with non-radioactive Re, Re-188, Tc-99m and Tc-99 incorporated directly into the peptide disulfide bond; (2) to correlate the in vitro receptor binding affinities of the Re and Tc-99 complexes to their three dimensional solution phase structures; (3) to evaluate the in vivo distributions and tumor-targeting properties of the Tc-99m- and Re-188-cyclized peptides with high receptor binding; and (4) to assess the radiotherapeutic potential of the optimal Re-188-coordinated peptide in a mouse model of pancreatic cancer.