| Breast cancer is the most prevalent form of cancer in U.S. women and the second leading cause of cancer-related deaths. Early detection of breast cancer is vital to the survival of the patient. Studies have shown that of the 64% of women diagnosed at a localized stage of breast cancer, 97% have a likelihood of survival over a five-year period. This is not the case if the cancer has spread regionally or distantly; the numbers now become 75% and 20%, respectively, over a five-year period. Just as early detection of tumors is essential for survival, so determination of estrogen receptor (ER) levels is vital for making the appropriate treatment choices of endocrine therapy vs. radiation and/or cytotoxic chemotherapy. In order to accomplish this, development of a ligand that contains a radioactive moiety and has high affinity for the ER is necessary. An attractive target comes in the form of 2-fluoroestradiol (I), which has been shown to have a relative binding affinity of 87% to the ER and 3700% to the sex-hormone binding globulin (SHBG); the native ligand estradiol (II) is set at a binding affinity of 100% for ER and has been set at 100% for SHBG.;The aromatic carbon-fluorine bond found in I is both advantageous and problematic from the standpoint of a chemist. The advantageous aspect is that this bond is highly stable and not likely to be cleaved in vivo, however this bond is problematic due to the limited number of reactions known to give a fluorine-18 to aromatic carbon bond. For the later reason, we sought out to incorporate the fluorine-18 via a diaryl iodonium salt precursor. Formation of the iodonium salt precursors was successfully accomplished, but reactivity towards fluorine could not be achieved with proper regiochemistry.;While imaging ER levels in tumors can be done using F-18 labeled estrogens it is important to develop receptor imaging agents labeled with the widely available and less expensive technetium-99m radionuclide. We have explored the synthesis and evaluation of metal carbonyl complexes with 1,4,7-triazacyclononane. The results have suggested that these complexes are not suitable for ER imaging. |
