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Molecular imaging of VEGF in gastrointestinal cancer in vivo using confocal laser endomicroscopy
  1. Sebastian Foersch1,
  2. Ralf Kiesslich1,
  3. Maximillian J Waldner2,
  4. Peter Delaney3,
  5. Peter R Galle1,
  6. Markus F Neurath2,
  7. Martin Goetz1
  1. 1Medical Clinic I, University of Mainz, Mainz, Germany
  2. 2Medical Clinic I, University of Erlangen, Erlangen, Germany
  3. 3Optiscan Pty, Ltd, Notting Hill, Victoria, Australia
  1. Correspondence to Martin Goetz, Medical Clinic I, Johannes Gutenberg-University of Mainz, Langenbeckstr. 1, D-55131 Mainz, Germany; mgoetz{at}mail.uni-mainz.de

Abstract

Background Vascular endothelial growth factor (VEGF) is a therapeutic target in gastrointestinal cancer (GiC). However, its in vivo visualisation could not be achieved to date with endoscopic techniques. Confocal laser endomicroscopy (CLE) is a novel imaging technique for gastrointestinal endoscopy providing in vivo microscopy at subcellular resolution. The aim of the study was to evaluate CLE for in vivo molecular imaging of VEGF in GiC.

Methods Molecular imaging of tumours in APCmin mice, in xenograft models and in surgical specimens of patients with colorectal cancer (CRC) was achieved after application of labelled antibodies. The tumour sites were scanned with the probe for the strongest specific fluorescent signal. From all tumour sites examined with CLE in vivo, targeted specimens were obtained for histology, immunohistochemistry (IHC) and fluorescence microscopy.

Results A VEGF-specific signal was visualised in vivo in 13/15 APCmin mice and in 9/10 xenograft tumours. CLE enabled the cytoplasmatic distribution of VEGF to be displayed due to its subcellular resolution. In human tissue, a VEGF-specific signal was observed in 12/13 malignant specimens and in 10/11 samples from healthy mucosa from the patients (p<0.03). CLE findings correlated well with ex vivo microscopy.

Conclusion In vivo molecular imaging with specific targeting of VEGF is possible in murine tumours, human xenografts and tissue specimens using CLE. CLE with similar probes can be performed in human colonoscopy. Therefore—from a technical point of view—in vivo molecular imaging is transferable to stratification of patients with CRC during endoscopy even today. CLE could contribute to the identification of lesions at risk and potentially predict response to targeted treatment.

  • Basic sciences
  • colorectal carcinoma
  • endoscopy
  • gastrointestinal cancer
  • imaging

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Footnotes

  • Funding This study has been supported by a government grant of the ‘Stiftung Rheinland-Pfalz für Innovation’ (961-38 62 61/821-Projekt 821) to MG. SF received student scholarships from the Boehringer-Ingelheim-Foundation and the Professional Association of German Internists. Aspects of this trial are part of the MD thesis of SF.

  • Competing interests Peter Delaney is Director of Technology at Optiscan Pty, Ltd, Notting Hill, Victoria, Australia.

  • Ethics approval This study was conducted with the approval of the ethics committee of Rheinland-Pfalz, Germany (no. 837.321.03).

  • Provenance and peer review Not commissioned; externally peer reviewed.

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