The optimal imaging window for dysplastic colorectal polyp detection using c-Met targeted fluorescence molecular endoscopy

Steven J de Jongh, Josephina P M Vrouwe, Floris J Voskuil, Iris Schmidt, Jessie Westerhof, Jan J Koornstra, Marieke L de Kam, Arend Karrenbeld, James C H Hardwick, Dominic J Robinson, Jacobus Burggraaf, Ingrid M C Kamerling, Wouter B Nagengast*

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

15 Citaten (Scopus)
48 Downloads (Pure)

Samenvatting

Fluorescence molecular endoscopy (FME) is an emerging technique that has the potential to improve the 22% colorectal polyp detection miss-rate. We determined the optimal dose-to-imaging interval and safety of FME using EMI-137, a c-Met-targeted fluorescent peptide, in a population at high risk for colorectal cancer. Methods: We performed in vivo FME and quantification of fluorescence by multidiameter single-fiber reflectance/single-fiber fluorescence spectroscopy in 15 patients with a dysplastic colorectal adenoma. EMI-137 was intravenously administered (0.13 mg/kg) at a 1-, 2- or 3-h dose-to-imaging interval (n = 3 patients per cohort). Two cohorts were expanded to 6 patients on the basis of target-to-background ratios. Fluorescence was correlated to histopathology and c-Met expression. EMI-137 binding specificity was assessed by fluorescence microscopy and in vitro experiments. Results: FME using EMI-137 appeared to be safe and well tolerated. All dose-to-imaging intervals showed significantly higher fluorescence in the colorectal lesions than in surrounding tissue, with a target-to-background ratio of 1.53, 1.66, and 1.74 for the 1-, 2-, and 3-h cohorts, respectively, and a mean intrinsic fluorescence of 0.035 vs. 0.023 mm-1 (P < 0.0003), 0.034 vs. 0.021 mm-1 (P < 0.0001), and 0.033 vs. 0.019 mm-1 (P < 0.0001), respectively. Fluorescence correlated with histopathology on a macroscopic and microscopic level, with significant c-Met overexpression in dysplastic mucosa. In vitro, a dose-dependent specific binding was confirmed. Conclusion: FME using EMI-137 appeared to be safe and feasible within a 1- to 3-h dose-to-imaging interval. No clinically significant differences were observed among the cohorts, although a 1-h dose-to-imaging interval was preferred from a clinical perspective. Future studies will investigate EMI-137 for improved colorectal polyp detection during screening colonoscopies.

Originele taal-2English
Pagina's (van-tot)1435-1441
Aantal pagina's7
TijdschriftJournal of Nuclear Medicine
Volume61
Nummer van het tijdschrift10
Vroegere onlinedatum20-mrt.-2020
DOI's
StatusPublished - 1-okt.-2020

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