TC-99M-LABELED LAMININ FRAGMENTS FOR CANCER IMAGING

THE OBJECTIVE IS DEVELOPMENT OF A RADIOPHARMACEUTICAL, USING A SYNTHETIC LAMININ NONAPEPTIDE RADIOLABELED WITH TC-9M, FOR DETECTION AND LOCALIZATION OF METASTATIC TUMOR CELLS OF EPITHELIAL ORIGIN. THE LAMININ NONAPEPTIDE WILL BE USED TO TARGET THE LAMININ RECEPTOR; LAMININ RECEPTORS ARE KNOWN TO HAVE AN INCREASED EXPRESSION IN HUMAN CANCERS, AND HUMAN COLON CANCER IN PARTICULAR. THIS SPECIFIC TRACER CAN BE USED IN BOTH ANIMAL AND HUMAN TUMOR MODELS, ALLOWING RATIONAL EXTRAPOLATION TO HUMANS. IN PHASE I, THE LAMININ NONAPEPTIDE WILL BE FORMULATED IN SINGLE-STEP, DIRECT LABELING KITS, AND THE BINDING OF THE TC-9M LABELED LAMININ TO TUMOR CELLS MEASURED, USING I-125-LABELED LAMININ AS A REFERENCE. BIODISTRIBUTION STUDIES WILL BE CONDUCTED IN NORMAL C57BL/6 MICE AND IN C57BL/6 MICE BEARING B16 MELANOMAS, WITH TUMOR IMAGING STUDIES IN ATHYMIC RATS BEARING XENO-GRAFTS OF THE HUMAN COLON CARCINOMA CELL LINE LOVO. IN PHASE II, EXTENDED ANIMAL STUDIES WILL BE CONDUCTED, PRODUCT FORMULATION AND MANUFACTURING PROTOCOLS DETERMINED, ACUTE TOXICITY STUDIES CONDUCTED AND, IF FEASIBLE, PRELIMINARY HUMAN STUDIES.