MICROMETER SPATIAL RESOLUTION IN SENSITIVE AND QUANTITATIVE BORON IMAGING OF TISSUES IN BORON NEUTRON CAPTURE THERAPY USING LARIS

CHEMICAL AND IMMUNOLOGICAL THERAPIES FOR CANCER OFFER PROMISE FOR CONTROLLING LIMITED NUMBERS OF SYSTEMICALLY DISPERSED TUMOR CELLS; HOWEVER, LOCALIZED TREATMENT MODALITIES ARE REQUIRED FOR MANY TUMOR TYPES THAT ARE UNRESPONSIVE TO CURRENT THERAPIES. BRAIN TUMORS, WHICH ARE PROTECTED BY THE BLOOD-BRAIN-BARRIER, REQUIRE ADDITIONAL EMPHASIS. BORON NEUTRON CAPTURE THERAPY (BNCT) RELIES ON THE CAPTURE OF A THERMAL NEUTRON BY BORON, WHICH HAS BEEN PRE-POSITIONED BIOCHEMICALLY IN THE TUMOR, FISSIONING INTO ENERGETIC LITHIUM IONS AND -PARTICLES. BECAUSE THE RANGE OF THESE FISSION FRAGMENTS IS RELATIVELY SMALL (I.E., FEW MUM), THE CLINICAL EFFICACY OF THE THERAPY IS GUARANTEED ONLY IF THE BORON IS POSITIONED IN A SENSITIVE AREA OF THE TUMOR CELL, SUCH AS THE CELL NUCLEUS. A MAJOR TECHNICAL ISSUE AFFECTING BNCT CLINICAL EFFICACY IS THE QUESTION OF BORON CONCENTRATION AND ITS VARIABILITY AS A FUNCTION OF INTER/INTRACELLULAR LOCATION. TO DATE, IT HAS NOT BEEN POSSIBLE TO ACCURATELY DETERMINE THE LOCATION AND QUANTITY OF BORON WITHIN AN INDIVIDUAL CELL AND TO DETERMINEITS VARIABILITY. SEVERAL TECHNIQUES SUCH AS ALPHA TRACK-ETCH AND SECONDARY ION MASS SPECTROMETRY (SIMS) HAVE BEEN USED TO LOCALIZE BORON IN CELLS. NEITHER TECHNIQUE HASBEEN TOTALLY SUCCESSFUL IN LOCATING AND QUANTIFYING BORON ACCURATELY IN INTRACELLULAR AREAS OF TISSUE SECTIONS AT CONCENTRATIONS OF INTEREST IN BNCT. RESONANCE IONIZATION SPECTROSCOPY (RIS), A NEW ULTRATRACE ELEMENT ANALYSIS TECHNIQUE, EMPLOYS PRECISELY TUNED LASERS TO IONIZE A CHOSENELEMENT EFFICIENTLY WITHOUT INTERFERENCE FROM THE PONDEROUSLY LARGER BACKGROUND OF OTHER CONSTITUENTS IN THE SAMPLE. RIS, WHEN COMBINED WITH LASER ATOMIZATION, LEADS TOA NEW ANALYTICAL TECHNIQUE, LASER ATOMIZATION, RESONANCE IONSPECTROSCOPY (LARIS), A TECHNIQUE THAT HAS ALMOST ALL OF THEADVANTAGES OF SIMS, YET REFLECTS SIGNIFICANT IMPROVEMENTS OVER SOME SIMS SHORTCOMINGS (E.G., SENSITIVITY, EFFICIENCY, AND ISOBARIC AND MOLECULAR INTERFERENCES). IN PHASE I, LARIS IS BEING USED TO LOCALIZE AND QUANTIFY THE BORON CONCENTRATION AND ITS VARIABILITY IN INTER- AND INTRACELLULAR AREAS. THIS TECHNIQUE WILL ENABLE QUANTIFIED MEASUREMENTS OF BORON CONCENTRATION AT THE PPM OR SUB-PPM LEVEL WITH MICROMETER SPATIAL RESOLUTION.