CELL TRACKING USING A NOVEL LINKER TECHNOLOGY

ZYNAXIS CELL SCIENCE, INC., HAS DEVELOPED FLUORESCENT CELL-TRACKING MOLECULES THAT BIND CELL MEMBRANES VIA A HIGH-AFFINITY LIPOPHILIC LINKER WITHOUT AFFECTING VIABILITY OR GROWTH. RADIONUCLIDE-CARRYING ANALOGS WOULD ALLOW CLINICAL USE OF THIS NOVEL TECHNOLOGY WITH MANY CELL TYPES TO FOLLOW MIGRATION OF HOST CELLS TO DISEASE SITES. THE SPECIFIC AIMS OF PHASE I ARE TO: (1) SYNTHESIZE A CELL-TRACKING AGENT CONTAINING A COVALENTLY BOUND GAMMA EMMITTER SUITABLE FOR SMALL-ANIMAL WHOLE-BODY IMAGING ((131)I-ZYN-1), AND (2) CHARACTERIZE ITS MEMBRANE-BINDING STABILITY AND EFFECTS ON ERYTHROCYTE AND LYMPHOCYTE VIABILITY AND FUNCTION IN VITRO AND ERYTHROCYTE LIFETIME IN VIVO. (131)I-ZYN-1 WILL HAVE IMMEDIATE COMMERCIAL VALUE FORSTUDIES OF CELL TRAFFICKING IN ANIMAL MODELS OF DISEASE (CANCER, THROMBOSIS, ATHEROSCLEROSIS, ARTHRITIS, INFLAMMATION). THE AIMS OF PHASE II WILL BE TO (1) TEST THE HYPOTHESIS THATMEMBRANE-BOUND RADIOIMAGING AGENTS ((131)I-ZYN-1) ARE LESS TOXIC THAN CURRENT IMAGING AGENTS THAT LOCALIZE IN THE CYTOPLASM, AND (2) DEVELOP ANALOGS COMBINING LIPOPHILIC LINKERS WITH CHELATORS FOR NUCLIDES USED IN CLINICAL IMAGING ((99M)TC, (111)IN, GD). CELLS LABELED WITH THE LATTER WILL BE APPLICABLE TO LOCALIZATION AND DISEASE MONITORING OF METASTATIC CANCER, THROMBOSIS, ATHEROSCLEROSIS, AUTOIMMUNE LESIONS, AND OCCULT INFECTION ORBLEEDING.