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Research ArticleOncology

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 and Wouter B. Nagengast
Journal of Nuclear Medicine October 2020, 61 (10) 1435-1441; DOI: https://doi.org/10.2967/jnumed.119.238790
Steven J. de Jongh
1Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, The Netherlands
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Josephina P.M. Vrouwe
2Centre for Human Drug Research, Leiden, The Netherlands
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Floris J. Voskuil
3Department of Oral and Maxillofacial Surgery, University Medical Center Groningen, Groningen, The Netherlands
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Iris Schmidt
1Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, The Netherlands
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Jessie Westerhof
1Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, The Netherlands
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Jan J. Koornstra
1Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, The Netherlands
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Marieke L. de Kam
2Centre for Human Drug Research, Leiden, The Netherlands
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Arend Karrenbeld
4Department of Pathology, University Medical Center Groningen, Groningen, The Netherlands
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James C.H. Hardwick
5Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands; and
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Dominic J. Robinson
6Center for Optical Diagnostics and Therapy, Department of Otorhinolaryngology and Head and Neck Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
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Jacobus Burggraaf
2Centre for Human Drug Research, Leiden, The Netherlands
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Ingrid M.C. Kamerling
2Centre for Human Drug Research, Leiden, The Netherlands
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Wouter B. Nagengast
1Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, The Netherlands
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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.

  • optimal imaging window
  • fluorescence molecular endoscopy
  • colorectal polyp detection
  • colorectal cancer
  • EMI-137 targeting c-Met

Footnotes

  • ↵* Contributed equally to this work.

  • ↵† Contributed equally to this work.

  • Published online Mar. 20, 2020.

  • © 2020 by the Society of Nuclear Medicine and Molecular Imaging.
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Journal of Nuclear Medicine: 61 (10)
Journal of Nuclear Medicine
Vol. 61, Issue 10
October 1, 2020
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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
Journal of Nuclear Medicine Oct 2020, 61 (10) 1435-1441; DOI: 10.2967/jnumed.119.238790

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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
Journal of Nuclear Medicine Oct 2020, 61 (10) 1435-1441; DOI: 10.2967/jnumed.119.238790
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Keywords

  • Optimal imaging window
  • Fluorescence molecular endoscopy
  • Colorectal polyp detection
  • colorectal cancer
  • EMI-137 targeting c-Met
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