CXCR4 peptide-based fluorescence endoscopy in a mouse model of Barrett’s esophagus

Background Near-infrared (NIR) fluorescence imaging has been emerging as a promising strategy to overcome the high number of early esophageal adenocarcinomas missed by white light endoscopy and random biopsy collection. We performed a preclinical assessment of fluorescence imaging and endoscopy using a novel CXCR4-targeted fluorescent peptide ligand in the L2-IL1B mouse model of Barrett’s esophagus. Methods Six L2-IL1B mice with advanced stage of disease (12–16 months old) were injected with the CXCR4-targeted, Sulfo-Cy5-labeled peptide (MK007), and ex vivo wide-field imaging of the whole stomach was performed 4 h after injection. Before ex vivo imaging, fluorescence endoscopy was performed in three L2-IL1B mice (12–14 months old) by a novel imaging system with two L2-IL1B mice used as negative controls. Results Ex vivo imaging and endoscopy in L2-IL1B mice showed that the CXCR4-targeted MK007 accumulated mostly in the dysplastic lesions with a mean target-to-background ratio > 2. The detection of the Sulfo-Cy5 signal in dysplastic lesions and its co-localization with CXCR4 stained cells by confocal microscopy further confirmed the imaging results. Conclusions This preliminary preclinical study shows that CXCR4-targeted fluorescence endoscopy using MK007 can detect dysplastic lesions in a mouse model of Barrett’s esophagus. Further investigations are needed to assess its use in the clinical setting.

Development of Dual-Scale Fluorescence Endoscopy for In Vivo Bacteria Imaging in an Orthotopic Mouse Colon Tumor Model

Colorectal cancer is a representative cancer where early diagnosis and proper treatment monitoring are important. Recently, cancer treatment using bacteria has actively progressed and has been successfully monitored using fluorescence imaging techniques. However, because subcutaneous tumor models are limited in reflecting the actual colorectal cancer situation, new imaging approaches are needed to observe cancers growing in the colon. The fluorescence endoscopic approach is an optimal monitoring modality to evaluate the therapeutic response of bacteria in orthotopic colon cancer. In this study, we developed dual-scaled fluorescence endoscopy (DSFE) by combining wide-field fluorescence endoscopy (WFE) and confocal fluorescence endomicroscopy (CFEM) and demonstrated its usefulness for evaluating bacterial therapy. Firstly, the endoscopic probe of DSFE was developed by integrating the CFEM probe into the guide sheath of WFE. Secondly, colorectal cancer tumor growth and tumors infiltrating the fluorescent bacteria were successfully monitored at the multi-scale using DSFE. Finally, the bacterial distribution of the tumor and organs were imaged and quantitatively analyzed using CFEM. DSFE successfully exhibited fluorescent bacterial signals in an orthotopic mouse colon tumor model. Thus, it can be concluded that the DSFE system is a promising modality to monitor bacterial therapy in vivo.