Development of Opioid Receptor Ligands for Oncology Studies - Our goal is to develop and validate radiolabeled opioid receptor ligands for use in oncology studies in vivo and in vitro, with emphasis upon imaging radioligands for PET and SPECT scanning. Endogenous opioid peptides and opioid receptors are expressed in a variety of human and animal tumors, including those of ectodermal, mesodermal and endodermal origin. Markers for localization of tumors expressing opioid receptors may have value as diagnostic aids, and would present opportunities for novel studies of the role played by opioids in neoplasia. Our group has extensive experience in the development and use of radioligands for studies of opioid receptors in non-tumoral pathologies. We now propose to apply this expertise to oncology investigations. Specifically, we propose preclinical work designed to develop imaging radioligands and an animal model that are suitable for in vivo studies of opioid receptors on mammary carcinomas. We propose: (1) to design, synthesize and chemically characterize novel opioid receptor ligands labeled with the imaging radionuclides I-123, Tc-99m or F-18; (2) to ascertain their affinity, selectivity and specificity for opioid receptor subtypes by in vitro assays using membranes from normal rodent brain and from a human breast cancer cell line (MCF-7); (3) to characterize their in vivo binding to opioid receptors in normal rodents and in animal models of mammary carcinoma; (4) to evaluate their pharmacokinetics and pharmacology in normal baboon by SPECT (I- 123, Tc-99m) or PET (F-18) imaging; and (5) to ascertain their suitability for imaging trials in human beings.
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