Detection of colonic dysplasia in vivo using a targeted heptapeptide and confocal microendoscopy.
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-microm working distance and 2.5-microm (transverse) and 20-microm (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.
Hsiung
Pei-Lin
PL
Department of Pediatrics, Radiology and Microbiology & Immunology, Stanford University School of Medicine, 318 Campus Dr., Rm. E-150, Stanford, California 94305, USA.
Hsiung
Pei-Lei
PL
Hardy
Jonathan
J
Friedland
Shai
S
Soetikno
Roy
R
Du
Christine B
CB
Wu
Amy P
AP
Sahbaie
Peyman
P
Crawford
James M
JM
Lowe
Anson W
AW
Contag
Christopher H
CH
Wang
Thomas D
TD
D000236:Adenoma / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D000595:Amino Acid Sequence; D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D003106:Colon / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D003111:Colonic Polyps / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D003113:Colonoscopy / Q000379:methods*; D019793:Fluorescein; D005456:Fluorescent Dyes; D006801:Humans; D018613:Microscopy, Confocal / Q000379:methods; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism; D019151:Peptide Library; D011230:Precancerous Conditions / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology
D014408:Biomarkers, Tumor; D005456:Fluorescent Dyes; D009842:Oligopeptides; D019151:Peptide Library; D019793:Fluorescein