Fluorescence grid analysis for the evaluation of piecemeal surgery in sinonasal inverted papilloma: a proof-of-concept study

• Published in: European journal of nuclear medicine and molecular imaging Vol. 49; no. 5; pp. 1640 - 1649
• Main Authors: Vonk, J, Voskuil, FJ, de Wit, JG, Heeman, WT, Nagengast, WB, van Dam, GM, Feijen, RA, Korsten-Meijer, AGW, van der Vegt, B, Witjes, MJH
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-04-2022; Springer Nature B.V
• Subjects: Bevacizumab; Bevacizumab - therapeutic use; Cardiology; Evaluation; Fluorescence; Fragments; Growth factors; Head & neck cancer; Head and Neck Neoplasms; Histopathology; Humans; Imaging; Immunohistochemistry; Medical imaging; Medicine; Medicine & Public Health; Nuclear Medicine; Oncology; Oncology – Head and Neck; Optical Imaging; Original; Original Article; Orthopedics; Papilloma; Papilloma, Inverted - diagnostic imaging; Papilloma, Inverted - metabolism; Papilloma, Inverted - surgery; Patients; Radiology; Signal processing; Surgery; Surgical instruments; Tumors; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - metabolism; Molecular imaging; Papilloma; Optical imaging; Vascular endothelial growth factor A; Inverted; Paranasal sinus neoplasms
• ISSN: 1619-7070; 1619-7089
• DOI: 10.1007/s00259-021-05567-x

Purpose
Local recurrence occurs in ~ 19% of sinonasal inverted papilloma (SNIP) surgeries and is strongly associated with incomplete resection. During surgery, it is technically challenging to visualize and resect all SNIP tissue in this anatomically complex area. Proteins that are overexpressed in SNIP, such as vascular endothelial growth factor (VEGF), may serve as a target for fluorescence molecular imaging to guide surgical removal of SNIP. A proof-of-concept study was performed to investigate if the VEGF-targeted near-infrared fluorescent tracer bevacizumab-800CW specifically localizes in SNIP and whether it could be used as a clinical tool to guide SNIP surgery.
Methods
In five patients diagnosed with SNIP, 10 mg of bevacizumab-800CW was intravenously administered 3 days prior to surgery. Fluorescence molecular imaging was performed in vivo during surgery and ex vivo during the processing of the surgical specimen. Fluorescence signals were correlated with final histopathology and VEGF-A immunohistochemistry. We introduced a fluorescence grid analysis to assess the fluorescence signal in individual tissue fragments, due to the nature of the surgical procedure (i.e., piecemeal resection) allowing the detection of small SNIP residues and location of the tracer ex vivo.
Results
In all patients, fluorescence signal was detected in vivo during endoscopic SNIP surgery. Using ex vivo fluorescence grid analysis, we were able to correlate bevacizumab-800CW fluorescence of individual tissue fragments with final histopathology. Fluorescence grid analysis showed substantial variability in mean fluorescence intensity (
FI
mean
), with SNIP tissue showing a median
FI
mean
of 77.54 (IQR 50.47–112.30) compared to 35.99 (IQR 21.48–57.81) in uninvolved tissue (
p
 < 0.0001), although the diagnostic ability was limited with an area under the curve of 0.78.
Conclusions
A fluorescence grid analysis could serve as a valid method to evaluate fluorescence molecular imaging in piecemeal surgeries. As such, although substantial differences were observed in fluorescence intensities, VEGF-A may not be the ideal target for SNIP surgery.
Trial registration
NCT03925285.