2022 Articles

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

Marcazzan, Sabrina; Braz Carvalho, Marcos J.; Konrad, Matthias; Strangmann, Julia; Tenditnaya, Anna; Baumeister, Theresa; Schmid, Roland M.; Wester, Hans-Jürgen; Ntziachristos, Vasilis; Gorpas, Dimitris; Wang, Timothy C.; Schottelius, Margret; Quante, Michael

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.