Elsevier

Gastrointestinal Endoscopy

Volume 68, Issue 3, September 2008, Pages 520-527
Gastrointestinal Endoscopy

Original article
Experimental endoscopy
Biochromoendoscopy: molecular imaging with capsule endoscopy for detection of adenomas of the GI tract

https://doi.org/10.1016/j.gie.2008.02.023Get rights and content

Background

Current capsule endoscopy (CE) provides minimally invasive technology for GI imaging but has limited ability to discriminate different types of polyps. Near infrared fluorescent (NIRF) probes activated by biomarkers upregulated in adenomas (eg, cathepsin B) are potentially powerful tools to distinguish premalignant or malignant lesions from benign or inflammatory lesions.

Objectives

To examine whether CE can be integrated with NIRF probes to detect adenomas and whether cathepsin B–activated NIRF probes are activated by benign or inflammatory lesions.

Design

Mouse models of adenomas, hyperplactic/lymphoid polyps, and acute or chronic intestinal inflammation were injected intravenously with a cathepsin B–activated probe (Prosense 680). Dissected intestine was imaged with CE under white or NIRF light. For NIRF excitation (680 nm), dichroic and emission (700 nm) filters were combined with CE when images were recorded. Prosense 680 samples with or without protease were used as positive and negative controls. CE-based imaging data were verified by using and independent imaging system (Xenogen IVIS system).

Main Outcome Measurements

Proof of principal that CE integrated with NIRF probes can detect and discriminate adenomas from other lesions.

Results

CE-based NIRF imaging with Prosense 680 readily visualized adenomas, including in the colitis model. NIRF signals of different intensities were detected. Prosense 680 was not activated by benign or inflammatory lesions.

Limitation

Optical filters external to the capsule were used.

Conclusions

We demonstrate proof of the principle that biochromoendoscopy—CE combined with molecular probes––provides a novel approach that differentiates adenomas from benign polyps and inflammatory lesions.

Section snippets

Animal models

A protocol for animal use in this study was approved by the University of North Carolina Institutional Animal Care and Use Committee. Mice carrying an inactivating Min mutation in the adenomatous polyposis coli gene (ApcMin/+ mice) were used as a well-characterized model of premalignant adenomatous colonic polyps.18ApcMin/+ mice on a C57BL6 background and normal wild-type (WT) littermates were purchased from Jackson Laboratories (Bar Harbor, Me) and expanded in our facility. For benign lesions

NIRF-integrated CE detects different intensity NIRF signals

Activated Prosense 680 (AP) was obtained by mixing 10 μL of 10 mmol/L Prosense 680 and 20 μL of 5% trypsin in 70 μL of PBS (pH 7.4) at room temperature. Different concentrations were achieved by 1:5 and 1:10 dilution in PBS. The NIRF-integrated CE was capable of detecting NIRF signal intensity across this 10-fold probe concentration difference (Fig. 3). This provided initial proof of principle that the modified CE system can detect NIRF.

Detection of adenomatous polyps in ApcMin/+ mice by modified CE

A white light image of a segment of Prosense 680 injected

Discussion

We have demonstrated proof of principle for biochromoendoscopy by integrating “molecular beacons” with NIRF imaging and conventional CE. Our modified CE was capable of detecting NIRF signals emitted from adenomatous polyps in intestines of ApcMin/+ mice injected with a cathepsin B–activatable probe. Importantly, such NIRF signals were specific to the precancerous adenomatous polyps. Benign growths such as hyperplastic polyps or lymphoid aggregates found in similarly treated SOCS2-HT/GH-TG or

Acknowledgments

We thank Dr Yijing Chen (Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC) for technical assistance.

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    Presented at Digestive Disease Week, Washington DC, May 23, 2007 (Gastrointest Endosc 2007;65:AB350).

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