SYNTHESIS OF IMAGABLE IODINATED ESTRADIOL - PHASE I

THE HIGH INCIDENCE OF BREAST CANCER IN WOMEN MAKES THIS DISEASE THE LEADING CANCER TYPE IN THIS POPULATION. THE PROPER STAGING OF THIS CANCER AND THE DETERMINATION OF THE PRESENCE OR ABSENCE OF ESTROGEN RECEPTORS PLAY MAJOR ROLES IN DETERMINING THE COURSE OF TREATMENT. PRESENTLY AVAILABLEMETHODS FOR SUCH STAGING AND ESTROGEN RECEPTOR IDENTIFICATION REQUIRE INVASIVE TECHNIQUES (SUCH AS SURGICALBIOPSY) AND "IN VITRO" ASSAYS. EXTERNAL IMAGING OF THESE TUMORS AND THEIR METASTASES BY USE OF A HIGHLY SPECIFIC ESTROGEN RECEPTOR - BINDING AGENT CONTAINING A SUITABLE RADIOISOTOPE WOULD BE VERY ADVANTAGEOUS BECAUSE OF ITS POTENTIAL SIMPLICITY, NON-INVASIVENESS AND SPEED. PREVIOUS RESEARCH WITH 17 B-ESTRADIOL POSSESSING (127)I (NATURAL NON-RADIOACTIVE IODINE) OR (125)I AT THE 16A POSITION ESTABLISHED THE HIGH ESTROGEN RECEPTOR SPECIFICITY, LOW NONSPECIFIC BINDING AND RELATIVELY SLOW METABOLIC DEGRADATION OF THIS COMPOUND. THE ISOTOPE (123)I (COMMERCIALLY AVAILABLE) HAS A Y-EMISSION ENERGY EXCELLENT FOR IMAGING WITH STANDARD NUCLEAR MEDICAL EQUIPMENT, BUT TO DATE, CANNOT BE EFFICIENTLY INTRODUCED INTO THE 16A POSITIONOF 17 B-ESTRADIOL BY THE METHODS CURRENTLY USED FOR (127)I OR (125)I, BECAUSE THE REACTION TIME REQUIRED FOR IODINATIONIS 1.5 - 2 TIMES THE HALF-LIFE OF (123)I (13H). THE OBJECTIVES OF THIS PROPOSED PHASE I WORK ARE TO DEVELOP A NEW SYNTHESIS OF 16A-I-17 B-ESTRADIOL AND ITS RAPID PURIFICATION, TO APPLY THIS SYNTHETIC METHOD TO THE PRODUCTION OF 16A-(123)I-17 B-ESTRADIOL, AND TO INVESTIGATE THE "IN VITRO" AND "IN VIVO" (RATS) PROPERTIES OF 16A-(123) I-17 B-ESTRADIOL IN ORDER TO ASSESS ITS SUITABILITY FOR THE IMAGING OF ESTROGEN RECEPTOR-POSITIVE VERSUS ESTROGEN RECEPTOR-NEGATIVE BREAST TUMORS AND METASTASES. THE WORK PERFORMED IN THIS PHASE WILL ALLOW THE DEVELOPMENT OF SYNTHETIC, BIOCHEMICAL AND IMAGING EXPERTISE WHICH WILL AID IN THE DEVELOPMENT OF RELATED (123)I-LABELED COMPOUNDS, SUCH AS PROGESTERONE AND TESTESTERONE ANALOGS OR DERIVATIVESWHICH MAY BE USEFUL IN THE CHARACTERIZATION OF OTHER TUMOR TYPES.