ULTRA SENSITIVE ANALYSIS FOR PT BY RIS IN TUMOR THERAPY

THE PLATINUM COMPOUND CISPLATIN IS WIDELY USED IN THE TREATMENT OF SOLID TUMORS. PRACTICAL PROBLEMS OF TOXICITY, DECREASING EFFICACY OVER TIME AND OTHER S ARISE, AND CAN BE ATTACKED MOST EFFECTIVELY THROUGH A BETTER KNOWLEDGE OF THE VARIOUS MECHANISMS INVOLVED, REQUIRING THE ABILITY TO MEASURE THE ACTIVE MATERIAL AT SITES OF INTEREST AND AT THE CONCENTRATION LEVELS EXISTING THERE. PRESENT ANALYTICAL TECHNIQUES ARE NOT SENSITIVE ENOUGH TO MONITOR THE ENTRANCE OF CISPLATIN INTO CELLS AND NUCLEI USING THE LIMITED AMOUNT OF BLOOD THAT CAN BE DRAWN IN SERIAL SAMPLES FROM PATIENTS. INTER-PATIENT STUDIES, FOR WHICH SMALL VARIATIONS IN VERY LOW LEVELS WOULD HAVE TO BE MEASURED, WOULD BE VERY DESIRABLE. AN EMERGING ANALYTICAL TECHNIQUE, RESONANCE IONIZATION SPECTROSCOPY (RIS), HAS DEMONSTRATED EXTREMELY HIGH SELECTIVITY AND SENSITIVITY IN ELEMENTAL ANALYSIS. RIS UTILIZES LASERS TUNED TO STATES UNIQUE TO THE DESIRED ELEMENT, THEREBY ACHIEVING EFFICIENT IONIZATION OF THE ANALYTE WITH ESSENTIALLY NO BACKGROUND. THESE CHARACTERISTICS ARE EXTENDABLE TO PLATINUM, AND WOULD PROVIDE A SOLUTION TO THE AIMS DESCRIBED ABOVE. INSTRUMENTAL AND CHEMICAL DEVELOPMENTS WILL APPLY THIS METHOD SPECIFICALLY TO PLATINUM IN BIOLOGICAL MATRICES. SAMPLE ATOMIZATION OPTIONS WILL BE INVESTIGATED TOGETHER WITH QUANTITATION OPTIONS, INCLUDING ISOTOPE DILUTION, TO MINIMIZE COMPLEXITY AND ASSURE RELIABILITY.