TY - JOUR T1 - The Optimal Imaging Window for Dysplastic Colorectal Polyp Detection Using c-Met–Targeted Fluorescence Molecular Endoscopy JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 1435 LP - 1441 DO - 10.2967/jnumed.119.238790 VL - 61 IS - 10 AU - Steven J. de Jongh AU - Josephina P.M. Vrouwe AU - Floris J. Voskuil AU - Iris Schmidt AU - Jessie Westerhof AU - Jan J. Koornstra AU - Marieke L. de Kam AU - Arend Karrenbeld AU - James C.H. Hardwick AU - Dominic J. Robinson AU - Jacobus Burggraaf AU - Ingrid M.C. Kamerling AU - Wouter B. Nagengast Y1 - 2020/10/01 UR - http://jnm.snmjournals.org/content/61/10/1435.abstract N2 - 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. ER -