1. The Optimal Imaging Window for Dysplastic Colorectal Polyp Detection Using c-Met-Targeted Fluorescence Molecular Endoscopy.
- Author
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de Jongh SJ, Vrouwe JPM, Voskuil FJ, Schmidt I, Westerhof J, Koornstra JJ, de Kam ML, Karrenbeld A, Hardwick JCH, Robinson DJ, Burggraaf J, Kamerling IMC, and Nagengast WB
- Subjects
- Aged, Colonic Polyps pathology, Colorectal Neoplasms pathology, Female, HT29 Cells, Humans, Male, Middle Aged, Adenoma diagnostic imaging, Colonic Polyps diagnostic imaging, Colonoscopy methods, Colorectal Neoplasms diagnostic imaging, Proto-Oncogene Proteins c-met metabolism, Spectrometry, Fluorescence methods
- Abstract
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., (© 2020 by the Society of Nuclear Medicine and Molecular Imaging.)- Published
- 2020
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