Molecular imaging in gastrointestinal endoscopy

Abstract

Molecular imaging is a rapidly growing new discipline in gastrointestinal endoscopy. It uses the molecular signature of cells for minimally-invasive, targeted imaging of gastrointestinal pathologies. Molecular imaging comprises wide field techniques for the detection of lesions and microscopic techniques for in vivo characterization. Exogenous fluorescent agents serve as molecular beacons and include labeled peptides and antibodies, and probes with tumor-specific activation. Most applications have aimed at improving the detection of gastrointestinal neoplasia with either prototype fluorescence endoscopy or confocal endomicroscopy, and first studies have translated encouraging results from rodent and tissue models to endoscopy in humans. Even with the limitations of the currently used approaches, molecular imaging has the potential to greatly impact on future endoscopy in gastroenterology.

Fig. 1

Comparison of different molecular probe classes

Fig. 2

Targeted detection of high-grade dysplasia in Barrett’s esophagus with fluorescence imaging. a) White light endoscopic image of Barrett’s esophagus shows absence of architectural features to guide biopsy for dysplasia. b) Molecular image after topical administration of labeled peptides shows increased fluorescence intensity at a site (arrow) of high-grade dysplasia. c) Binding of the peptide to the outer surface of the dysplastic crypts can be seen on fluorescence microscopy. d) Corresponding histology (H&E) at 20X magnification.

Fig. 3

In living mice after orthotopic tumor implantation, white light and NIR images captured with a prototype microcatheter show a small, flat adenocarcinoma. The whitish lesion in a) demonstrates strong NIR signal in b), reflecting protease activity after tumor specific activation of a molecular probe, which is absent in the surrounding healthy mucosa. c) shows white light images with false color overlays for tumor location. (reproduced from(10) with permission of the publisher.)

Fig. 4

In vivo fluorescence image collected at border of a) colonic adenoma with confocal miniprobe demonstrates selective binding of a fluorescein-labeled peptides selected from a phage library(4) and shows specific affinity to b) dysplastic crypts (left) in comparison to adjacent normal mucosa (right). Scale bars, 20 μm.

Fig. 5

a) Full body fluorescent imaging of a human colorectal cancer xenograft in a nude mouse identifies the EGFR positive tumor in the right groin after injection of labeled monoclonal antibodies. b) In vivo confocal endomicroscopy of the xenograft visualizes the binding of the fluorescently labeled antibodies. c) Ex vivo immunohistochemistry confirms the EGFR overexpression on cancer cells. Scale bars 30μm.