Sulfonamide derivative targeting carbonic anhydrase IX as a nuclear imaging probe for colorectal cancer detection in vivo

Siao Syun Guan, Chun Chia Cheng, Ai Sheng Ho, Chia Chi Wang, Tsai Yueh Luo, Tse Zung Liao, Jungshan Chang, Cheng Tien Wu, Shing Hwa Liu

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)36139-36155
Number of pages17
JournalOncotarget
Volume6
Issue number34
DOIs
Publication statusPublished - 2015

Fingerprint

Sulfonamides
Colorectal Neoplasms
Thiophenes
Neoplasms
Indium Radioisotopes
Heterografts
Serum
Carbonic Anhydrase IX
Cell Hypoxia
Indium
Nuclear Medicine
Tumor Biomarkers
Radioisotopes
Cell Survival
Biomarkers
Fluorescence
Growth

Keywords

  • Carbonic anhydrase IX
  • Colorectal cancer
  • Radioisotope-labeled
  • Sulfonamide

ASJC Scopus subject areas

  • Oncology

Cite this

Guan, S. S., Cheng, C. C., Ho, A. S., Wang, C. C., Luo, T. Y., Liao, T. Z., ... Liu, S. H. (2015). Sulfonamide derivative targeting carbonic anhydrase IX as a nuclear imaging probe for colorectal cancer detection in vivo. Oncotarget, 6(34), 36139-36155. https://doi.org/10.18632/oncotarget.5684

Sulfonamide derivative targeting carbonic anhydrase IX as a nuclear imaging probe for colorectal cancer detection in vivo. / Guan, Siao Syun; Cheng, Chun Chia; Ho, Ai Sheng; Wang, Chia Chi; Luo, Tsai Yueh; Liao, Tse Zung; Chang, Jungshan; Wu, Cheng Tien; Liu, Shing Hwa.

In: Oncotarget, Vol. 6, No. 34, 2015, p. 36139-36155.

Research output: Contribution to journalArticle

Guan, Siao Syun ; Cheng, Chun Chia ; Ho, Ai Sheng ; Wang, Chia Chi ; Luo, Tsai Yueh ; Liao, Tse Zung ; Chang, Jungshan ; Wu, Cheng Tien ; Liu, Shing Hwa. / Sulfonamide derivative targeting carbonic anhydrase IX as a nuclear imaging probe for colorectal cancer detection in vivo. In: Oncotarget. 2015 ; Vol. 6, No. 34. pp. 36139-36155.
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