Feasibility of bevacizumab-IRDye800CW as a tracer for fluorescence-guided meningioma surgery

Bianca M Dijkstra*, Julie Nonnekens, Wouter Nagengast, Schelto Kruijff, Gert Jan Meersma, Wilfred F A den Dunnen, Frank A E Kruyt, Rob J M Groen

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Scopus)


OBJECTIVE: Meningiomas are frequently occurring, often benign intracranial tumors. Molecular fluorescence can be used to intraoperatively identify residual meningioma tissue and optimize safe resection; however, currently no clinically approved agent is available for this specific tumor type. In meningiomas, vascular endothelial growth factor α (VEGFα) is upregulated, and this biomarker could be targeted with bevacizumab-IRDye800CW, a fluorescent agent that is already clinically applied for the resection of other tumors and neoplasms. Here, the authors investigated the feasibility of using bevacizumab-IRDye800CW to target VEGFα in a CH-157MN xenografted mouse model.

METHODS: Five mice with CH-157MN xenografts with volumes of 500 mm3 were administered intravenous bevacizumab-IRDye800CW. Mice were imaged in vivo at 24 hours, 48 hours, and 72 hours after injection with the FMT2500 fluorescence imaging system. Biodistribution was determined ex vivo using the Pearl fluorescent imager at 72 hours after injection. To mimic a clinical scenario, 2 animals underwent postmortem xenograft resection using both white-light and fluorescence guidance. Lastly, fresh and frozen human meningioma specimens were incubated ex vivo with bevacizumab-IRDye800CW, stained with anti-VEGFα, and microscopically examined.

RESULTS: In vivo, tumors fluoresced at all time points after tracer administration and background fluorescence decreased with time. Ex vivo analyses of tracer biodistribution showed the highest fluorescence in resected tumor tissue. Brain, skull, and muscle tissue showed very low fluorescence. Microscopically, fluorescence was observed in the cytoplasm and was correlated with VEGFα expression patterns. During postmortem surgery, both the tumor bulk and a small tumor remnant were detected. Bevacizumab-IRDye800CW bound specifically to all tested human meningioma samples, as indicated by a high fluorescent signal in the tumor bulk compared with the surrounding healthy dura mater.

CONCLUSIONS: Bevacizumab-IRDye800CW showed meningioma specificity, as illustrated by high VEGFα-mediated uptake in the meningioma xenograft mouse model. Small tumor lesions were detected using fluorescence guidance. Thus, the next step will be to assess the feasibility of using already available clinical grade bevacizumab-IRDye800CW to optimize meningioma resection in a human trial.

Original languageEnglish
Pages (from-to)1263-1272
Number of pages10
JournalJournal of Neurosurgery
Issue number5
Early online date28 Oct 2022
Publication statusPublished - May 2023

Bibliographical note

Funding Information:
Dr. Dijkstra receives research grants from the University of Groningen, the University Medical Center Groningen, and the Stichting de Cock-Hadders.

Publisher Copyright:
©AANS 2023, except where prohibited by US copyright law.


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