1170318-30-5Relevant articles and documents
Synthesis and SAR of novel Re/99mTc-Labeled benzenesulfonamide carbonic anhydrase IX inhibitors for molecular imaging of tumor hypoxia
Lu, Genliang,Hillier, Shawn M.,Maresca, Kevin P.,Zimmerman, Craig N.,Eckelman, William C.,Joyal, John L.,Babich, John W.
supporting information, p. 510 - 520 (2013/04/10)
Carbonic anhydrase IX (CA-IX) is upregulated in cancer in response to the hypoxic tumor microenvironment, making it an attractive molecular target for the detection of hypoxic solid tumors. A series of small molecule benzenesulfonamide based CA-IX inhibitors containing novel tridentate chelates complexed with the M(CO)3 core (M = Re or 99mTc) were designed and synthesized. The in vitro binding affinity of the benzenesulfonamide rhenium complexes yielded IC50 values ranging from 3 to 116 nM in hypoxic CA-IX expressing HeLa cells. One of the most potent compounds, 3d (IC50 = 9 nM), was radiolabeled with technetium tricarbonyl ({99mTc(CO)3}+) to afford the {99mTc(CO)3}+ complex in excellent yield and high purity. 99mTc(CO)3-3d bound specifically to CA-IX expressing hypoxic HeLa cells. This effort led to the identification of a diverse series of promising high affinity {99mTc(CO) 3}+ radiolabeled CA-IX inhibitors with the potential to significantly impact diagnosis, staging, and treatment selection of hypoxic solid tumors.
