Cyclopentadienyl Rhenium (Technetium) Tricarbonyl Complexes Integrated in Estrogen Receptor Ligands for ER+ Tumor Imaging

摘要

A class of breast tumors, known as ER+, contains significant concentrations of ER which functions to regulate cell growth, and mediate the action of estrogen antagonists. There is a need for the development non- invasive and reliable methods for the determination of tumor ER concentration in the identification of patients predicted to respond to hormone therapy. It has been shown that tumor ER concentration can be determined by imaging, using 18F-labeled ER selective ligands, and that the ER concentrations determined by imaging correlate well with those determined by immunoassay methods on surgical biopsies. Because of the short half-life of fluorine-18, this method is costly, with low availability. Thus, the development of an effective ER imaging agent that is of low cost and widespread availability might eliminate the need for tumor biopsy in the treatment selection for breast cancer patients. We propose the development of radiopharmaceutical imaging agents labeled with 99mTc, which is available at most hospitals at a relatively low cost, as a 99Mo/99mTc generator. Studies conducted in this laboratory suggest that an integrated organometallic design in which technetium bonded to carbon forms a part of the core structure will display the stability, as well the requisite affinity to ER.