Technical Report abstract
Nature Medicine 14, 454 - 458 (2008)
Published online: 16 March 2008 | Corrected online: 21 March 2008 | doi:10.1038/nm1692
There is an Erratum (May 2008) associated with this Technical Report.
Detection of colonic dysplasia in vivo using a targeted heptapeptide and confocal microendoscopy
Pei-Lin Hsiung1, Jonathan Hardy1, Shai Friedland2,3, Roy Soetikno2,3, Christine B Du1, Amy P Wu1, Peyman Sahbaie2, James M Crawford4, Anson W Lowe3, Christopher H Contag1 & Thomas D Wang2,3
A combination of targeted probes and new imaging technologies provides a powerful set of tools with the potential to improve the early detection of cancer. To develop a probe for detecting colon cancer, we screened phage display peptide libraries against fresh human colonic adenomas for high-affinity ligands with preferential binding to premalignant tissue. We identified a specific heptapeptide sequence, VRPMPLQ, which we synthesized, conjugated with fluorescein and tested in patients undergoing colonoscopy. We imaged topically administered peptide using a fluorescence confocal microendoscope delivered through the instrument channel of a standard colonoscope. In vivo images were acquired at 12 frames per second with 50-
m working distance and 2.5-
m (transverse) and 20-
m (axial) resolution. The fluorescein-conjugated peptide bound more strongly to dysplastic colonocytes than to adjacent normal cells with 81% sensitivity and 82% specificity. This methodology represents a promising diagnostic imaging approach for the early detection of colorectal cancer and potentially of other epithelial malignancies.
- Department of Pediatrics, Radiology and Microbiology & Immunology, Stanford University School of Medicine, 318 Campus Dr., Rm. E-150, Stanford, California 94305, USA.
- Veterans Affairs Palo Alto Health Care System, 3801 Miranda Ave., Bldg. 100, Palo Alto, California 94304, USA.
- Department of Medicine, Stanford University School of Medicine, 300 Pasteur Dr., Alway Bldg., Rm. M211, Stanford, California 94305, USA.
- Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, P.O. Box 100275, 1600 SW Archer Rd., MSB 649, Gainesville, Florida 32610, USA.
Correspondence to: Thomas D Wang2,3 e-mail: thomaswa@umich.edu
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