Bigott Heather M, Parent Ephraim, Luyt Leonard G, Katzenellenbogen John A, Welch Michael J
Division of Radiological Sciences, Washington University School of Medicine, 510 S. Kingshighway, Campus Box 8225, St. Louis, Missouri 63110, USA.
Bioconjug Chem. 2005 Mar-Apr;16(2):255-64. doi: 10.1021/bc049770g.
Cyclopentadienyl tricarbonylmetal (CpTM, M = Re, (94m)Tc) complexes, some based on a typical nonsteroidal estrogen, were prepared with the aim of developing technetium- and rhenium-labeled imaging agents for estrogen receptor (ER) positive breast tumors. CpT[(94m)Tc] compounds with simple cyclopentadienyl substituents were first synthesized using a modified double ligand transfer reaction. The in vivo biodistribution of one of these CpT[(94m)Tc] complexes was determined by tissue dissection and microPET imaging. Novel C-ring substituted analogues of cyclofenil, a nonsteroidal compound known to bind the ER, were also prepared, and their ER binding was measured. Because of their low ER affinity, however, labeling and imaging studies of these compounds were not pursued. It is notable that the highest ER binding analogue, a CpTRe cyclofenil derivative, could be synthesized from the corresponding ferrocenyl cyclofenil analogue by the double ligand transfer reaction. This further demonstrates the versatility of the double ligand transfer reaction and indicates that the synthesis of technetium and rhenium radiolabeled agents for breast tumor imaging and therapy is also likely to be successful.
制备了环戊二烯基三羰基金属（CpTM，M = Re，(94m)Tc）配合物，其中一些基于典型的非甾体雌激素，目的是开发用于雌激素受体（ER）阳性乳腺肿瘤的锝和铼标记成像剂。首先使用改良的双配体转移反应合成了具有简单环戊二烯基取代基的CpT[(94m)Tc]化合物。通过组织解剖和微型正电子发射断层扫描（microPET）成像确定了其中一种CpT[(94m)Tc]配合物的体内生物分布。还制备了环芬尼（一种已知可结合ER的非甾体化合物）的新型C环取代类似物，并测量了它们与ER的结合。然而，由于它们与ER的亲和力较低，因此未对这些化合物进行标记和成像研究。值得注意的是，最高ER结合类似物，即一种CpTRe环芬尼衍生物，可以通过双配体转移反应从相应的二茂铁基环芬尼类似物合成。这进一步证明了双配体转移反应的通用性，并表明用于乳腺肿瘤成像和治疗的锝和铼放射性标记剂的合成也可能成功。
