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 available methods for such staging and estrogen receptor identification require invasive techniques (such as surgical biopsy) 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, noninvasiveness and speed.Previous research with 17 b-estradiol possessing 127 I (natural non-radioactive iodine) or I at the 16a position established the high estrogen receptor specificity, low nonspecific binding and relatively slow metabolic degradation of this compound. The isotope I (commercially available) has a Y-emission energy excellent for imaging with standard nuclear medical equipment but, to date, cannot be efficienti@@ntrodrifd into the 16a position of 17 b-estradiol by the methods currently used for I or 123 1 because the reaction time required for iodination is 1.5-2 times the half-life of I (I 3h).The objectives of Phase I are to develop a new synthesis of 16a-123 1-17 b-estradiol and its rapid purification, to apply this synthetic method to the production of IV - 1-17 b-IVO 123-estradiol, and to investigate the in vitro and in viv (rats) properties of 16a-1-17 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 IP4 chemical and imaging expertise which will aid in the development of related I-labeled compounds, such as progesterone and testosterone analogs or derivatives, which may be useful in the characterization of other tumor types.
Thesaurus Terms: Chemical Synthesis, Design And Production (General), Diagnosis, Diagnostic Tests, Design, Development And Evaluation Of Diagnostic Tests, Estratriene Series, Estradiol, Neoplasms Diagnosis, Breast Neoplasms Diagnosis, Mammography, Neoplasms Diagnosis, Radioisotope Diagnosis, Neoplasms Of Reproductive System, Breast Neoplasms, Optics, Imaging-Visualization (General), Radiodiagnosis And Radiodiagnostic Methods, Radioisotopes, Iodine, Radiopharmacology Chemical Reactions, Substitution, Nucleophilic, Chemical Structure, Stereochemistry, Estratriene Series, Estrogens, Neoplasms Classification And Staging, Neoplastic Growth, Neoplasms Metastasis, Optics, Image Enhancement, Pyridines, Radioautography, Radionuclide Scanning, Receptors Of Non-Sensory Stimuli (General), Sulfonates, Thyroid Gland Chemistry, Analytical Methods, Spectrometry, Ultraviolet, Mammals, Rodents, Myomorpha, Rats (Laboratory), Physical Separation, Chromatography, High Pressure Liquid
