In vivo targeting of colonic dysplasia on fluorescence endoscopy with near-infrared octapeptide
- 1Department of Medicine, Division of Gastroenterology, Ann Arbor, Michigan, USA
- 2Department of Biomedical Engineering, Ann Arbor, Michigan, USA
- Correspondence to Dr Thomas D Wang, Associate Professor of Medicine and Biomedical Engineering, Division of Gastroenterology, University of Michigan, USA;
Contributors Designed research: ZL, SJM, BPJ, TDW; performed research: ZL, SJM, BPJ; contributed new reagents or analytic tools: SJM, BPJ; analysed data: ZL, SJM, BPJ, TDW; wrote the paper: ZL, SJM, BPJ, TDW.
- Revised 17 January 2012
- Accepted 3 February 2012
- Published Online First 17 March 2012
Objective To demonstrate a near-infrared (NIR) peptide that is highly specific for colonic adenomas on fluorescence endoscopy in vivo.
Design A 3 mm diameter endoscope was adapted to deliver 671 nm illumination and collect NIR fluorescence (696–736 nm). Target (QPIHPNNM) and control (YTTNKH) peptides were labelled with Cy5.5, a NIR dye, and characterised by mass spectra. The peptides were topically administered separately (100 μM) through the endoscope's instrument channel into the distal colon of CPC;Apc mice, genetically engineered to spontaneously develop adenomas. After 5 min for incubation, the unbound peptides were rinsed off, and images were collected at a rate of 10 frames/s. Regions of interest were identified around the adenoma and adjacent normal-appearing mucosa on white light. Intensity measurements were made from these same regions on fluorescence, and the target-to-background ratio (TBR) was calculated.
Results An image resolution of 9.8 μm and field of view of 3.6 mm was achieved at a distance of 2.5 mm between the distal end of the instrument and the tissue surface. On mass spectra, the experimental mass-to-charge ratio for the Cy5.5-labelled target and control peptides agreed with expected values. The NIR fluorescence images of adenomas revealed individual dysplastic crypts with distorted morphology. By comparison, only amorphous surface features could be visualised from reflected NIR light. The average TBR for adenomas was found to be 3.42±1.30 and 1.88±0.38 for the target and control peptides, respectively, p=0.007.
Conclusion A NIR peptide was shown to be highly specific for colonic adenomas on fluorescence endoscopy in vivo and to achieve sub-cellular resolution images.
- Colorectal adenomas
- molecular pathology
- colon carcinogenesis
- colonic adenomas
- Barrett's metaplasia
- Barrett's oesophagus
- fluorescence endoscopy
- oesophageal cancer
- colorectal cancer screening
- gastrointestinal endoscopy
- gastrointestinal neoplasia
Funding This research was supported in part by National Institutes of Health (NIH) U54 CA136429, P50 CA93990, R01 CA142750 to TDW.
Competing interests The University of Michigan has filed a provisional patent on behalf of authors SJM, BPJ and TDW on the peptide presented in this study.
Patient consent Obtained.
Ethics approval Ethics approval was approved by University of Michigan Institutional Review Board.
Provenance and peer review Not commissioned; externally peer reviewed.