title: Fluorescence-based endoscopic imaging of Thomsen-Friedenreich antigen to improve early detection of colorectal cancer.
abstract: Thomsen-Friedenreich (TF) antigen belongs to the mucin-type tumor-associated carbohydrate antigen. Notably, TF antigen is overexpressed in colorectal cancer (CRC) but is rarely expressed in normal colonic tissue. Increased TF antigen expression is associated with tumor invasion and metastasis. In this study, we sought to validate a novel nanobeacon for imaging TF-associated CRC in a preclinical animal model. We developed and characterized the nanobeacon for use with fluorescence colonoscopy. In vivo imaging was performed on an orthotopic rat model of CRC. Both white light and fluorescence colonoscopy methods were utilized to establish the ratio-imaging index for the probe. The nanobeacon exhibited specificity for TF-associated cancer. Fluorescence colonoscopy using the probe can detect lesions at the stage which is not readily confirmed by conventional visualization methods. Further, the probe can report the dynamic change of TF expression as tumor regresses during chemotherapy. Data from this study suggests that fluorescence colonoscopy can improve early CRC detection. Supplemented by the established ratio-imaging index, the probe can be used not only for early detection, but also for reporting tumor response during chemotherapy. Furthermore, since the data obtained through in vivo imaging confirmed that the probe was not absorbed by the colonic mucosa, no registered toxicity is associated with this nanobeacon. Taken together, these data demonstrate the potential of this novel probe for imaging TF antigen as a biomarker for the early detection and prediction of the progression of CRC at the molecular level.
authors: Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka, Japan.
authors: Shinji
authors: S
authors: Sakuma
authors: James Y H
authors: JY
authors: Yu
authors: Timothy
authors: T
authors: Quang
authors: Ken-Ichiro
authors: K
authors: Hiwatari
authors: Hironori
authors: H
authors: Kumagai
authors: Stephanie
authors: S
authors: Kao
authors: Alex
authors: A
authors: Holt
authors: Jalysa
authors: J
authors: Erskind
authors: Richard
authors: R
authors: McClure
authors: Michael
authors: M
authors: Siuta
authors: Tokio
authors: T
authors: Kitamura
authors: Etsuo
authors: E
authors: Tobita
authors: Seiji
authors: S
authors: Koike
authors: Kevin
authors: K
authors: Wilson
authors: Rebecca
authors: R
authors: Richards-Kortum
authors: Eric
authors: E
authors: Liu
authors: Kay
authors: K
authors: Washington
authors: Reed
authors: R
authors: Omary
authors: John C
authors: JC
authors: Gore
authors: Wellington
authors: W
authors: Pham
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000378:metabolism; D000818:Animals; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D003952:Diagnostic Imaging / Q000379:methods*; D055088:Early Detection of Cancer; D005260:Female; D005453:Fluorescence; D005456:Fluorescent Dyes; D007124:Immunoenzyme Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D054118:Nanospheres; D051381:Rats; D011923:Rats, Nude; D014407:Tumor Cells, Cultured
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; D014408:Biomarkers, Tumor; D005456:Fluorescent Dyes; C016467:Thomsen-Friedenreich antigen
keywords: Thomsen-Friedenreich antigen; antigen; biomarker; cancer imaging; colonoscopy; colorectal cancer; fluorescence; molecular imaging; nanotechnology; optical imaging