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, non-invasiveness and speed. Previous research with 17Beta-estradiol possessing 127I (natural non-radioactive iodine) or 125I at the 16Alpha position established the high estrogen receptor specificity, low nonspecific binding and relatively slow metabolic degradation of this compound. The isotope 123I (commercially available) has a Y-emission energy excellent for imaging with standard nuclear medical equipment, but to date, cannot be efficiently introduced into the 16Alpha position of 17Beta-estradiol by the methods currently used for 127I or 125I, because the reaction time required for iodination is 1.5-2 times the half-life of 123I (13h). The objects of this proposed Phase I work are to develop a new synthesis of 16Alpha-I-17Beta-estradiol and its rapid purification, to apply this synthetic method to the production of 16Alpha-123I-17Beta-estradiol, and to investigate the in vitro and in vivo(rats) properties of 16Alpha-123I-17Beta-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 123I-labeled compounds, such as progesterone and testesterone analogs or derivatives, which may be useful in the characterization of other tumor types.
| Holt, J A; Artwohl, J E; Mercer, L J et al. (1991) Biodistribution, with high uptake by the reproductive tract, of an intraperitoneally infused radiohalogenated steroidal estrogen-receptor ligand. Int J Radiat Oncol Biol Phys 20:567-73 |
| Anderson, R E; Holt, J A (1989) Binding of radiolabeled estrogens by human cells in vitro: implications to the development of a new diagnostic and therapeutic modality in the treatment of malignancies with estrogen receptors. Gynecol Oncol 34:80-3 |
