THE PROPOSED PHASE I PROGRAM WILL EVALUATE THE APPLICABILITY OF NEWLY AVAILABLE ULTRA-HIGH BRIGHTNESS X-RAY SOURCE FACILITIES (SYNCHROTRON LIGHT SOURCES) TO CANCER RELATED PROBLEMS IN CELL BIOLOGY AND MORPHOLOGY.

THE PROPOSED PHASE I PROGRAM WILL EVALUATE THE APPLICABILITY OF NEWLY AVAILABLE ULTRA-HIGH BRIGHTNESS X-RAY SOURCE FACILITIES (SYNCHROTRON LIGHT SOURCES) TO CANCER RELATED PROBLEMS IN CELL BIOLOGY AND MORPHOLOGY. IN PARTICULAR, POTENTIAL APPLICATIONS IN THE AREAS OF ONCOGENESIS, EARLY CANCER DIAGNOSIS, AND CANCER THERAPY WILL BE EXAMINED. THIS PROPOSAL IS DIRECTED TO THE NATIONAL CANCER INSTITUTE FOR CONSIDERATION BY THE DIVISION OF CANCER BIOLOGY AND DIAGNOSIS. THE SYNCHROTRON LIGHT SOURCE WILL ALLOW IMAGING AND ANALYSIS OF TRACE METALS IN CELLS AT CONCENTRATION LEVELS FAR BELOW THOSE PREVIOUSLY VISUALIZABLE. IT IS EXPECTED THAT, USING AN X-RAY MICROPROBE BEAM LINE, TRACE METAL CONCENTRATIONS AT LEVELS OF INTEREST WILL BE MEASURABLE WITH SPATIAL RESOLUTIONS OF APPROXIMATELY ONE MICRON. THE EXTREME BRIGHTNESS (INTENSITY PER UNIT SOLID ANGLE) OF THE SYNCHROTRON LIGHT SOURCE ALLOWS EFFECTIVE TUNING OF THE ENERGY OF X-RAYS STRIKING THE SAMPLE. BY THIS SOURCE ENERGY SELECTION, ONE CAN MAXIMIZE FLUORESCENCE EFFICIENCIES FOR THE TRACE METALS OF INTEREST, WHILE MINIMIZING BACKGROUND INTERFERENCES. AMONG APPLICATIONS OF THE ANALYTICAL TECHNIQUE TO BE EXAMINED IN PHASE I ARE ONCOGENESIS ASSOCIATED WITH METAL TOXICITY, LYMPHOCYTE FERRITIN ANALYSIS IN THE EARLY DIAGNOSIS OF BREAST CANCER, AND PLATINUM AND OTHER METAL COMPLEXES AS USED IN CANCER THERAPY. PHASE I WILL DEFINE WHICH APPLICATION HAS GREATEST POTENTIAL AND WILL INCLUDE FEASIBILITY MEASUREMENTS ON SAMPLES OF INTEREST USING AN ELECTRON MICROPROBE FACILITY, WITH FOLLOW-UP PRELIMINARY INVESTIGATIONS AT THE CORNELL SYNCHROTRON X-RAY FACILITY (CHESS). PHASE II WILL PROVIDE COMPLETE EXPERIMENTAL VERIFICATION OF ONE OR MORE OF THESE APPLICATIONS AT ONE OF THE AVAILABLE SYNCHROTRON X-RAY SOURCE FACILITIES. PHOTOMETRICS, IN ADDITION TO HAVING THE REQUISITE RESEARCH CAPABILITIES, IS THE LARGEST COMMERCIAL LABORATORY IN THE EASTERN US PROVIDING SCANNING ELECTRON MICROSCOPY, ELECTRON MICROPROBE, AND OTHER MICROANALYTICAL SERVICES. IT IS UNIQUELY POSITIONED TO PROVIDE A SIMILAR COMMERCIAL SERVICE AS THE INTERFACE BETWEEN THE CLINICAL OR LIFE SCIENCE USER AND THE SYNCHROTRON X-RAY RESOURCE. THE PHASE III PROGRAM WILL INCLUDE THE OFFERING OF THIS COMMERCIAL SYNCHROTRON X-RAY ANALYTICAL SERVICE.