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Theranostics 2018; 8(6):1458-1467. doi:10.7150/thno.22033 This issue Cite

Research Paper

Potential Red-Flag Identification of Colorectal Adenomas with Wide-Field Fluorescence Molecular Endoscopy

Elmire Hartmans^1*, Jolien J.J. Tjalma^1*, Matthijs D. Linssen^1,2, Pilar Beatriz Garcia Allende³, Marjory Koller⁴, Annelies Jorritsma-Smit², Mariana e Silva de Oliveira Nery¹, Sjoerd G. Elias⁵, Arend Karrenbeld⁶, Elisabeth G.E. de Vries⁷, Jan H. Kleibeuker¹, Gooitzen M. van Dam^4,8, Dominic J. Robinson⁹, Vasilis Ntziachristos³, Wouter B. Nagengast^1✉

1. Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
2. Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
3. Institute for Biological and Medical Imaging, Technical University of Munich and Helmholtz Center Munich, Munich, Germany
4. Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
5. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands
6. Department of Pathology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
7. Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
8. Department of Nuclear Medicine and Molecular Imaging and Intensive Care, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
9. Otolaryngology and Head & Neck Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
* E.H. and J.J.J.T contributed equally to this work.

✉ Corresponding author: Wouter B. Nagengast, MD Ph.D., Department of Gastroenterology and Hepatology, University Medical Center Groningen, PO box 30.001, 9700 RB, Groningen, the Netherlands; Phone: +31 50 361 2620; Fax: +31 50 361 9306; E-mail: w.b.nagengastnl. More

Abstract

Adenoma miss rates in colonoscopy are unacceptably high, especially for sessile serrated adenomas / polyps (SSA/Ps) and in high-risk populations, such as patients with Lynch syndrome. Detection rates may be improved by fluorescence molecular endoscopy (FME), which allows morphological visualization of lesions with high-definition white-light imaging as well as fluorescence-guided identification of lesions with a specific molecular marker. In a clinical proof-of-principal study, we investigated FME for colorectal adenoma detection, using a fluorescently labelled antibody (bevacizumab-800CW) against vascular endothelial growth factor A (VEGFA), which is highly upregulated in colorectal adenomas.

Methods: Patients with familial adenomatous polyposis (n = 17), received an intravenous injection with 4.5, 10 or 25 mg of bevacizumab-800CW. Three days later, they received NIR-FME.

Results: VEGFA-targeted NIR-FME detected colorectal adenomas at all doses. Best results were achieved in the highest (25 mg) cohort, which even detected small adenomas (<3 mm). Spectroscopy analyses of freshly excised specimen demonstrated the highest adenoma-to-normal ratio of 1.84 for the 25 mg cohort, with a calculated median tracer concentration in adenomas of 6.43 nmol/mL. Ex vivo signal analyses demonstrated NIR fluorescence within the dysplastic areas of the adenomas.

Conclusion: These results suggest that NIR-FME is clinically feasible as a real-time, red-flag technique for detection of colorectal adenomas.

Keywords: optical molecular imaging, spectroscopy, vascular endothelial growth factor a, near-infrared fluorescence.

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