title: Sulfonamide derivative targeting carbonic anhydrase IX as a nuclear imaging probe for colorectal cancer detection in vivo.
abstract: Hypoxic microenvironment is a common situation in solid tumors. Carbonic anhydrase IX (CA9) is one of the reliable cellular biomarkers of hypoxia. The role of CA9 in colorectal cancer (CRC) remains to be clarified. CA9 inhibitor such as sulfonamides is known to block CA9 activation and reduce tumor growth consequently. Here, we aimed to investigate the CA9 expression in serum and tumor from different stages of CRC patients and utilize sulfonamide derivative with indium-111 labeling as a probe for CRC nuclear imaging detection in vivo. The serum CA9 was correlated with the tumor CA9 levels in different stages of CRC patients. Hypoxia increased cell viability and CA9 expression in colorectal cancer HCT-15 cells. Sulfonamide derivative 5-(2-aminoethyl)thiophene-2-sulfonamide (ATS) could bind with CA9 in vitro under hypoxia. Moreover, tumor tissues in HCT-15-induced xenograft mice possessed higher hypoxic fluorescence signal as compared with other organs. We also found that the radioisotope signal of indium-111 labeled ATS, which was utilized for CRC detection in HCT-15-induced xenograft mice, was markedly enhanced in tumors as compared with non-ATS control. Taken together, these findings suggest that CA9 is a potential hypoxic CRC biomarker and measurement of serum CA9 can be as a potential tool for diagnosing CA9 expressions in CRC clinical practice. The radioisotope-labeled sulfonamide derivative (ATS) may be useful to apply in CRC patients for nuclear medicine imaging.
authors.affiliation: Institute of Nuclear Energy Research, Atomic Energy Council, Taoyuan, Taiwan.|Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Siao-Syun
authors.initials: SS
authors.lastname: Guan
authors.affiliation: Institute of Nuclear Energy Research, Atomic Energy Council, Taoyuan, Taiwan.|Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chun-Chia
authors.initials: CC
authors.lastname: Cheng
authors.affiliation: Division of Gastroenterology, Cheng Hsin General Hospital, Taipei, Taiwan.
authors.forename: Ai-Sheng
authors.initials: AS
authors.lastname: Ho
authors.affiliation: Division of Hepatology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and School of Medicine, Tzu Chi University, Hualien, Taiwan.
authors.forename: Chia-Chi
authors.initials: CC
authors.lastname: Wang
authors.affiliation: Institute of Nuclear Energy Research, Atomic Energy Council, Taoyuan, Taiwan.
authors.forename: Tsai-Yueh
authors.initials: TY
authors.lastname: Luo
authors.affiliation: Institute of Nuclear Energy Research, Atomic Energy Council, Taoyuan, Taiwan.
authors.forename: Tse-Zung
authors.initials: TZ
authors.lastname: Liao
authors.affiliation: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Jungshan
authors.initials: J
authors.lastname: Chang
authors.affiliation: Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Cheng-Tien
authors.initials: CT
authors.lastname: Wu
authors.affiliation: Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan.|Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan.|Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Shing-Hwa
authors.initials: SH
authors.lastname: Liu
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000097:blood*; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000097:blood*; D015687:Cell Hypoxia / Q000502:physiology; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000473:pathology; D003952:Diagnostic Imaging / Q000379:methods*; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011877:Radionuclide Imaging; D013449:Sulfonamides / Q000737:chemistry* / Q000493:pharmacokinetics
chemical_list: D000951:Antigens, Neoplasm; D013449:Sulfonamides; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases
keywords: carbonic anhydrase IX; colorectal cancer; radioisotope-labeled; sulfonamide