The Optimal Imaging Window for Dysplastic Colorectal Polyp Detection Using c-Met–Targeted Fluorescence Molecular Endoscopy

Journal of Nuclear Medicine, vol. 61, pp. 1435–1441

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.

Authors 13

1. Steven Jakob de Jongh

   University Medical Center Groningen

   Affiliation as printed

   Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, The Netherlands

2. Josephina P. M. Vrouwe Aachen Centre for Human Drug Research (CHDR)

   Centre for Human Drug Research

   Affiliation as printed

   Centre for Human Drug Research, Leiden, The Netherlands

3. Floris Jan Voskuil

   University Medical Center Groningen

   Affiliation as printed

   Department of Oral and Maxillofacial Surgery, University Medical Center Groningen, Groningen, The Netherlands

4. Iris W. Schmidt

   University Medical Center Groningen

   Affiliation as printed

   Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, The Netherlands

5. Jessie Westerhof

   University Medical Center Groningen

   Affiliation as printed

   Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, The Netherlands

6. Jan Jacob Koornstra

   University Medical Center Groningen

   Affiliation as printed

   Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, The Netherlands

7. Marieke L. de Kam Aachen Centre for Human Drug Research (CHDR)

   Centre for Human Drug Research

   Affiliation as printed

   Centre for Human Drug Research, Leiden, The Netherlands

8. Arend Karrenbeld

   University Medical Center Groningen

   Affiliation as printed

   Department of Pathology, University Medical Center Groningen, Groningen, The Netherlands

9. James C.H. Hardwick Aachen Department of Gastroenterology and Hepatology

   Leiden University Medical Center

   Affiliation as printed

   Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands; and

   Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands

10. Dominic J. Robinson

    Erasmus MC Cancer Institute

    Affiliation as printed

    Center for Optical Diagnostics and Therapy, Department of Otorhinolaryngology and Head and Neck Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands

11. Jacobus Burggraaf Aachen Centre for Human Drug Research (CHDR)

    Centre for Human Drug Research

    Affiliation as printed

    Centre for Human Drug Research, Leiden, The Netherlands

12. Ingrid M. C. Kamerling Aachen Centre for Human Drug Research (CHDR)

    Centre for Human Drug Research

    Affiliation as printed

    Centre for Human Drug Research, Leiden, The Netherlands

13. Wouter Bastiaan Nagengast

    University Medical Center Groningen

    Affiliation as printed

    Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, The Netherlands w.b.nagengast@umcg.nl

    Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, The Netherlands