Radiochemical synthesis and tissue distribution of Tc-99m-labeled 7 alpha-substituted estradiol complexes

The diagnosis and staging of breast cancer could be improved by the develop ment of radiopharmaceutical imaging agents that provide a noninvasive deter mination of the estrogen receptor (ER) status of tumor cells. Agents labele d with Tc-99m would be especially valuable in this regard. In attempting to achieve this goal, we synthesized four Tc-99m labeled 7 alpha-substituted estradiol complexes. One complex utilizes the "3+1" mixed ligand design to introduce the Tc metal, whereas the other three took advantage of the cyclo pentadienyltricarbonylmetal (CpTM) design. The Tc moieties were attached to the 7 alpha position of estradiol with a hexyl tether, a monoether tether, or a polyether tether, The corresponding rhenium compounds have binding af finities for the ER of 20-45% compared with estradiol. Radiochemical yields of the Tc-99m labeled compounds ranged from approximately 15% for the CpT- Tc complexes to 95% for the 3+1 inorganic complex. Tissue distribution stud ies in immature fe male rats showed low nonreceptor-mediated uptake in the target organs and high uptake in nontarget organs such as the liver and fat . These complexes represent the first time that estradiol has been labeled at the 7 alpha position with Tc-99m and provide a further refinement of our understanding of Ligand structure-binding affinity correlations for the ER . NUCL MED BIOL 27;3:269-278, 2000. (C) 2000 Elsevier Science Inc. All righ ts reserved.