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Near-infrared fluorescence molecular endoscopy detects dysplastic oesophageal lesions using topical and systemic tracer of vascular endothelial growth factor A
  1. Wouter B Nagengast1,
  2. Elmire Hartmans1,
  3. Pilar B Garcia-Allende2,
  4. Frans T M Peters1,
  5. Matthijs D Linssen1,3,
  6. Maximilian Koch2,
  7. Marjory Koller4,
  8. Jolien J J Tjalma1,
  9. Arend Karrenbeld5,
  10. Annelies Jorritsma-Smit3,
  11. Jan H Kleibeuker1,
  12. Gooitzen M van Dam4,6,
  13. Vasilis Ntziachristos2
  1. 1 Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center, Groningen, The Netherlands
  2. 2 Chair for Biological Imaging and Institute for Biological and Medical Imaging, Technical University of Munich and Helmholtz Centre Munich, Munich, Germany
  3. 3 Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center, Groningen, The Netherlands
  4. 4 Department of Surgery, University of Groningen, University Medical Center, Groningen, The Netherlands
  5. 5 Department of Pathology, University of Groningen, University MedicalCenter, Groningen, The Netherlands
  6. 6 Department of Nuclear Medicine & Molecular Imaging and Intensive Care, University of Groningen, University Medical Center, Groningen, The Netherlands
  1. Correspondence to Dr Wouter B Nagengast, Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center, Groningen, The Netherlands; w.b.nagengast{at}umcg.nl

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The incidence of oesophageal adenocarcinoma (EAC) is steeply rising. Early lesion detection is a critical factor for improving disease prognosis. We developed and investigated wide-field near-infrared fluorescence molecular endoscopy (NIR-FME), using systemic and topical administration of a fluorescence-labelled antibody against vascular endothelial growth factor (VEGFA). Fourteen patients with Barrett’s oesophagus (BE) underwent endoscopic mucosal resection (EMR) combined with NIR-MFE. From a total of 20 confirmed aberrant lesions identified with NIR-FME, 4 lesions were missed by high-definition (HD) narrowband imaging (NBI) and white-light endoscopy (WLE). This overall 25% detection enhancement advocates NIR-FME as a promising ‘red-flag’ technique for improving early oesophageal lesion detection. ClinicalTrials.gov ID NCT02129933. 

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Worldwide, >450 000 people are diagnosed with oesophageal cancer each year. In the western world, at least 80% of these cancers concern EAC.1–4 Late-stage disease detection challenges the efficacy of therapies, resulting in 400 000 deaths each year. Therefore, there is a pressing need for new endoscopic techniques that enable early EAC detection. Endoscopic imaging of targeted fluorescent agents directed against cancer-specific cellular and subcellular moieties, that is, fluorescence molecular endoscopy (FME), has been heralded as a novel method for oesophageal dysplasia and cancer detection.5 FME enables surface and subsurface visualisation of cancer-specific pathophysiology, going beyond the surface-only morphology and tissue discolourations visible with HD-WLE.6–10

In this study, we investigated for the first time real-time NIR-FME of EAC and dysplasia. A pilot study in patients with BE was based on a novel custom-built NIR fluorescence endoscope, paired to a HD-WL clinical scope (online supplementary figure 1) and employed the anti-VEGFA antibody bevacizumab, labelled with the NIR-fluorescent 800CW. The potential of VEGFA as an early discriminating target in BE was first confirmed by immunohistochemistry, demonstrating that all dysplastic tissues expressed VEGFA (online supplementary figure 2).

Supplementary file 1

[SP1.pdf]

The study furthermore compared systemic versus topical tracer administration during clinical inspection of …

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