PT  - JOURNAL ARTICLE
AU  - van Ginkel, Ymke
AU  - van der Heijst, Lisanne
AU  - Kats-Ugurlu, Gursah
AU  - Robinson, Domenic
AU  - Gorpas, Dimitris
AU  - Gabriëls, Ruben
AU  - Nagengast, Wouter
TI  - <strong>Oral administration of bevacizumab-800CW and cetuximab-800CW for the detection of early esophageal neoplastic lesions by quantitative fluorescence molecular endoscopy</strong>
DP  - 2024 Jun 01
TA  - Journal of Nuclear Medicine
PG  - 242111--242111
VI  - 65
IP  - supplement 2
4099  - http://jnm.snmjournals.org/content/65/supplement_2/242111.short
4100  - http://jnm.snmjournals.org/content/65/supplement_2/242111.full
SO  - J Nucl Med2024 Jun 01; 65
AB  - 242111 Introduction: Patients with Barrett’s esophagus (BE) have an increased risk of developing esophageal adenocarcinoma (EAC) and therefore surveillance is necessary. However, lesion detection with high-definition white light endoscopy (HD-WLE) and narrow-band imaging (NBI) is hampered by high miss rates. Previous phase II studies have confirmed the great potential of quantitative fluorescence molecular endoscopy (qFME) in combination with topically administered fluorescent tracers for lesion detection in BE. However, incubation time after topical tracer administration prolongs the procedure time by five minutes. In this ongoing clinical study, oral administration of bevacizumab-800CW, targeting vascular endothelial growth factor A (VEGFA), and cetuximab-800CW, targeting epidermal growth factor receptor (EGFR), is evaluated to improve both lesion detection and the clinical implementation of qFME. Methods: A total of 25 patients with BE scheduled for a diagnostic and/or therapeutic endoscopy will be included. First 5 – 10 patients receive 4.5 mg and/or 9 mg oral bevacizumab-800CW before qFME. Subsequently, five patients will be included who receive 4.5 mg cetuximab-800CW orally before the diagnostic endoscopy, before their therapeutic endoscopy they receive a dose of 9 mg. The patients drink the tracer in two sips in an upright position ten minutes before qFME. qFME consisted of in vivo fluorescence signal visualization and quantification by multi-diameter single fiber reflectance / single fiber fluorescence (MDSFR/SFF) spectroscopy measurements on the mucosa. Additionally, biopsies are collected from non-dysplastic Barrett tissue and (suspected) dysplastic tissue and ex vivo analysis will be performed.Results: Nine patients received 4.5 mg and/or 9 mg bevacizumab-800CW and two patients received 4.5 mg cetuximab-800CW. Oral administration of both tracers was well tolerated by patients. Higher fluorescence signal was seen in all visible lesion in vivo. All endoscopically visible lesions (n = 13) were detected by qFME with bevacizumab-800CW and cetuximab-800CW and were pathologically confirmed to be dysplastic. With further analysis in vivo target-to-background ratios and/or contrast-to-noise ratios and quantitative in vivo fluorescence based on MDSFR/SFF spectroscopy will be evaluated and visualized.Conclusions: Our preliminary results show that qFME with oral administration of bevacizumab-800CW and cetuximab-800CW is feasible and, compared to topical administration, seems promising for shortening the procedure time, while remaining adequate in lesion detection. We will extend the cetuximab-800CW cohort to five patients. The optimal dose and tracer will be determined and compared to combined administration of both tracers in five patients. Lastly, depending on what achieves the best in vivo results, either the optimal tracer or a combination of both tracers will be administered to five patients with non-dysplastic Barrett’s esophagus to test the specificity of our tracers.