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Detection of colonic dysplasia in vivo using a targeted heptapeptide and confocal microendoscopy.

ABSTRACT: 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.

SUBMITTER: Hsiung PL

PROVIDER: S-EPMC3324975 | biostudies-literature | 2008 Apr

REPOSITORIES: biostudies-literature

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Detection of colonic dysplasia in vivo using a targeted heptapeptide and confocal microendoscopy.

Hsiung Pei-Lin 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

Nature medicine 20080316 4

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 ...[more]

PMID: 18345013

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Project description:ObjectiveIn vivo Corneal Confocal Microscopy (IVCCM) is a validated, non-invasive test for diabetic sensorimotor polyneuropathy (DSP) detection, but its utility is limited by the image analysis time and expertise required. We aimed to determine the inter- and intra-observer reproducibility of a novel automated analysis program compared to manual analysis.MethodsIn a cross-sectional diagnostic study, 20 non-diabetes controls (mean age 41.4±17.3y, HbA1c 5.5±0.4%) and 26 participants with type 1 diabetes (42.8±16.9y, 8.0±1.9%) underwent two separate IVCCM examinations by one observer and a third by an independent observer. Along with nerve density and branch density, corneal nerve fibre length (CNFL) was obtained by manual analysis (CNFLMANUAL), a protocol in which images were manually selected for automated analysis (CNFLSEMI-AUTOMATED), and one in which selection and analysis were performed electronically (CNFLFULLY-AUTOMATED). Reproducibility of each protocol was determined using intraclass correlation coefficients (ICC) and, as a secondary objective, the method of Bland and Altman was used to explore agreement between protocols.ResultsMean CNFLManual was 16.7±4.0, 13.9±4.2 mm/mm2 for non-diabetes controls and diabetes participants, while CNFLSemi-Automated was 10.2±3.3, 8.6±3.0 mm/mm2 and CNFLFully-Automated was 12.5±2.8, 10.9 ± 2.9 mm/mm2. Inter-observer ICC and 95% confidence intervals (95%CI) were 0.73(0.56, 0.84), 0.75(0.59, 0.85), and 0.78(0.63, 0.87), respectively (p = NS for all comparisons). Intra-observer ICC and 95%CI were 0.72(0.55, 0.83), 0.74(0.57, 0.85), and 0.84(0.73, 0.91), respectively (p<0.05 for CNFLFully-Automated compared to others). The other IVCCM parameters had substantially lower ICC compared to those for CNFL. CNFLSemi-Automated and CNFLFully-Automated underestimated CNFLManual by mean and 95%CI of 35.1(-4.5, 67.5)% and 21.0(-21.6, 46.1)%, respectively.ConclusionsDespite an apparent measurement (underestimation) bias in comparison to the manual strategy of image analysis, fully-automated analysis preserves CNFL reproducibility. Future work must determine the diagnostic thresholds specific to the fully-automated measure of CNFL.

Dataset Information

Detection of colonic dysplasia in vivo using a targeted heptapeptide and confocal microendoscopy.

Publications

Detection of colonic dysplasia in vivo using a targeted heptapeptide and confocal microendoscopy.

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