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

Molecular Imaging of Colorectal Tumors by Targeting Colon Cancer Secreted Protein-2 (CCSP-2).
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Kim J, Do EJ, Moinova H, Bae SM, Kang JY, Hong SM, Fink SP, Joo J, Suh YA, Jang SJ, Hwang SW, Park SH, Yang DH, Ye BD, Byeon JS, Choe J, Yang SK, Markowitz SD, Kim SY, Myung SJ,


Kim J, Do EJ, Moinova H, Bae SM, Kang JY, Hong SM, Fink SP, Joo J, Suh YA, Jang SJ, Hwang SW, Park SH, Yang DH, Ye BD, Byeon JS, Choe J, Yang SK, Markowitz SD, Kim SY, Myung SJ, (click to view)

Kim J, Do EJ, Moinova H, Bae SM, Kang JY, Hong SM, Fink SP, Joo J, Suh YA, Jang SJ, Hwang SW, Park SH, Yang DH, Ye BD, Byeon JS, Choe J, Yang SK, Markowitz SD, Kim SY, Myung SJ,

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Neoplasia (New York, N.Y.) 2017 09 0419(10) 805-816 pii S1476-5586(17)30177-X
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.

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