99M TC-PHA-L4 LABELED LYMPHOCYTES

THE OBJECTIVE OF THE STUDY IS TO DEVELOP A PAN-T-LYMPHOCYTE 99MTC-RADIOTRACER WHICH CAN BE USED TO STUDY TRAFFICKING OF STIMULATED LYMPHOCYTES AND AS A DIAGNOSTIC RADIOPHARMACEUTICAL FOR CHRONIC INFECTIONS SUCH AS OSTEOMYELITIS AND FOR GRANULOMATOUS DISEASES. THE PLANT-DERIVED ISOLECTIN, PHYTOHEMAGGLUTININ-L4 (PHA-L4), BINDS THE CD3 RECEPTOR ON T-LYMPHOCYTES OF BOTH LABORATORY ANIMALS AND HUMANS. IT ALSO STIMULATES THE LYMPHOCYTES TO DIFFERENTIATE AND DIVIDE, SO THAT LABELED PHA-L4 WILL PROVIDE A TRACER FOR TRACKING STIMULATED LYMPHOCYTES. IN PHASE I, PHA-L4 WILL BE LABELED WITH 99MTC BY USING DIAMINEDITHIOL BIFUNCTIONAL CHELATES, WITH 125I LABELING AS A CONTROL FOR THE LABELING PROCESS. WE WILL MEASURE BINDING OF THE RADIOLABELED ISOLECTIN TO LYMPHOCYTES FROM SEVERAL SPECIES. BIODISTRIBUTION STUDIES WILL BE CONDUCTED IN MICE WITH INDUCED FOCAL ABSCESSES, USING 111IN OXINE-LABELED WBCS AS A BASELINE MEASURE OF WHITE CELL LABELING. THIS STUDY WILL RESULT IN A SIMPLE RADIOLABELING KIT, ALLOWING IN VIVO TAGGING OF CELLS. IN PHASE II, STUDIES WILL BE EXTENDED TO LARGER SPECIES, AND WILL INCLUDE BOTH INFLAMMATORY LESION AND TUMOR-BEARING ANIMALS.