RT Journal Article
SR Electronic
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
FD Society of Nuclear Medicine
SP 1435
OP 1441
DO 10.2967/jnumed.119.238790
VO 61
IS 10
A1 Steven J. de Jongh
A1 Josephina P.M. Vrouwe
A1 Floris J. Voskuil
A1 Iris Schmidt
A1 Jessie Westerhof
A1 Jan J. Koornstra
A1 Marieke L. de Kam
A1 Arend Karrenbeld
A1 James C.H. Hardwick
A1 Dominic J. Robinson
A1 Jacobus Burggraaf
A1 Ingrid M.C. Kamerling
A1 Wouter B. Nagengast
YR 2020
UL http://jnm.snmjournals.org/content/61/10/1435.abstract
AB 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.