title: Synthesis and binding affinities of Re(I) and (99m)Tc(I)-containing 16alpha-substituted estradiol complexes: Models for potential breast cancer imaging agents.
abstract: To develop technetium and rhenium-labeled imaging agents for estrogen receptor (ER) positive breast tumors, we have synthesized tridentate metal tricarbonyl chelates substituted at the 16alpha-position of estradiol. Their structures were characterized by IR, (1)H NMR, (13)C NMR, HRMS or elemental analysis. The rhenium complex 7b showed the highest ER binding affinity (RBA=25.7) among these compounds, so ligand 6b was selected to be labeled by the precursor [(99m)Tc(H(2)O)(3)(CO)(3)](+) to yield technetium(I)-99m complex 7b' with good radiochemical yields. The lipophilicity of corresponding technetium(I)-99m complex 7b' was appropriately reduced, which might be favorable to target tissue selectivity in vivo. The stability of complex 7b' is excellent in 1mM histidine, 1mM cysteine, PBS and bovine serum within 6h in vitro.
authors.affiliation: Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Liliang
authors.initials: L
authors.lastname: Huang
authors.forename: Hua
authors.initials: H
authors.lastname: Zhu
authors.forename: Yuanqing
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Xu
authors.forename: Wei
authors.initials: W
authors.lastname: Cui
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.forename: Yu-Mei
authors.initials: YM
authors.lastname: Shen
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D002417:Cattle; D003952:Diagnostic Imaging / Q000379:methods*; D004958:Estradiol / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D015609:Organotechnetium Compounds / Q000737:chemistry*; D011485:Protein Binding; D012211:Rhenium / Q000737:chemistry*
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D015609:Organotechnetium Compounds; D004958:Estradiol; D012211:Rhenium