Molecular Imaging of Colorectal Tumors by Targeting Colon Cancer Secreted Protein-2 (CCSP-2).

Abstract

A versatile biomarker for detecting colonic adenoma and colon cancer has yet to be developed. Colon cancer secreted protein-2 (CCSP-2) is a protein specifically expressed and secreted in colon adenomas and cancers. We developed a fluorescent imaging method based on CCSP-2 targeting for a more sensitive and specific detection of colorectal tumors. CCSP-2 expression was evaluated in human colon adenoma and colorectal specimens. Anti-CCSP-2 antibody was labeled with a near-infrared fluorescent dye, FPR-675, and molecular imaging of surgical human colorectal tumors was performed. Immunohistochemistry identified CCSP-2 expression in 87.0% of colorectal cancer specimens and 89.5% of colon adenoma specimens. Fluorescence imaging of surgical human colon specimens after spraying treatment with the probe permitted a clear distinction of cancer from paired normal colon tissue (target-to-background ratio, 4.09±0.42; P<.001). CCSP-2 targeting imaging was also evaluated in patient-derived colon cancer xenograft mouse and liver metastasis murine models. CCSP-2-positive colon cancer xenografts and liver metastases were visualized by near-infrared fluorescence imaging after intravenous injection of the probe, which showed significantly higher fluorescence. Our results show that CCSP-2 is a promising marker for colorectal tumor detection in clinical settings and that a CCSP-2-targeting molecular imaging strategy might improve the diagnosis of colorectal tumors in metastatic or recurrent cancers and aid in early colonoscopic detection of premalignant lesions.

• Authors: Jaeil Kim, Eun-Ju Do, Helen Moinova, Sang Mun Bae, Ja Young Kang, Seung-Mo Hong, Stephen P Fink, Jinmyoung Joo, Young-Ah Suh, Se Jin Jang, Sung Wook Hwang, Sang Hyoung Park, Dong-Hoon Yang, Byong Duk Ye, Jeong-Sik Byeon, Jaewon Choe, Suk-Kyun Yang, Sanford D Markowitz, Sang-Yeob Kim, Seung-Jae Myung
• Journal: Neoplasia (New York, N.Y.) (Neoplasia) Vol. 19 Issue 10 Pg. 805-816 (Oct 2017) ISSN: 1476-5586 [Electronic] United States
• PMID: 28886423 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers, Tumor
• Calcium-Binding Proteins
• Fluorescent Dyes
• VWA2 protein, human

Topics

• Animals
• Biomarkers, Tumor (genetics, metabolism)
• Calcium-Binding Proteins
• Cell Line, Tumor
• Colorectal Neoplasms (diagnostic imaging, genetics, metabolism, pathology)
• Disease Models, Animal
• Fluorescent Dyes
• Gene Expression
• Heterografts
• Humans
• Immunohistochemistry
• Male
• Mice
• Microscopy, Confocal
• Molecular Imaging (methods)
• Neoplasm Metastasis
• Protein Binding
• Tumor Burden