Journal of Medicinal Chemistry p. 6431 - 6443 (2016)
Update date:2022-08-25
Topics:
Sneddon, Deborah
Niemans, Raymon
Bauwens, Matthias
Yaromina, Ala
Van Kuijk, Simon J. A.
Lieuwes, Natasja G.
Biemans, Rianne
Pooters, Ivo
Pellegrini, Paul A.
Lengkeek, Nigel A.
Greguric, Ivan
Tonissen, Kathryn F.
Supuran, Claudiu T.
Lambin, Philippe
Dubois, Ludwig
Poulsen, Sally-Ann
Tumor hypoxia contributes resistance to chemo- and radiotherapy, while oxygenated tumors are sensitive to these treatments. The indirect detection of hypoxic tumors is possible by targeting carbonic anhydrase IX (CA IX), an enzyme overexpressed in hypoxic tumors, with sulfonamide-based imaging agents. In this study, we present the design and synthesis of novel gallium-radiolabeled small-molecule sulfonamides targeting CA IX. The compounds display favorable in vivo pharmacokinetics and stability. We demonstrate that our lead compound, [68Ga]-2, discriminates CA IX-expressing tumors in vivo in a mouse xenograft model using positron emission tomography (PET). This compound shows specific tumor accumulation and low uptake in blood and clears intact to the urine. These findings were reproduced in a second study using PET/computed tomography. Small molecules investigated to date utilizing 68Ga for preclinical CA IX imaging are scarce, and this is one of the first effective 68Ga compounds reported for PET imaging of CA IX.
View MoreChongqing KonAo Health Co.,Ltd
Contact:13687578375
Address:wuhan hubei china
Shanghai Yuantai Chemical Products Co., Ltd
Contact:021--66129803
Address:Chengyin Road,Shanghai,China
Jinan Hongfangde Pharmatech Co.,Ltd
Contact:86-531-88870908
Address:F Bldg. West Unit North Area of Univ. Tech. Garden Xinyu Rd. Jinan New & High Tech Industry Development Zone Shandong, China
Jiangsu Zhenfang Chemical CO.,LTD.(Suzhou Zhenfang Chemical Factory)
Contact:+86-512-69598882
Address:Room1201, Jiayuan Road No.1018, Xiangcheng District, Suzhou, China
Baoding City Light Industry And Textiles Imp.& Exp. Corp. Chemical Department.
Contact:86-312-3262436
Address:NO.658 CHAOYANG SOUTH STREET,BAODING CITY HEBEI CHINA
Doi:10.1135/cccc2009560
(2010)Doi:10.1021/jo00324a033
(1981)Doi:10.1039/c0nj00722f
(2011)Doi:10.1021/acs.inorgchem.9b03351
(2020)Doi:10.1016/j.cattod.2015.04.008
(2016)Doi:10.1002/adsc.201000266
(2010)