Feasibility of bevacizumab-IRDye800CW as a tracer for fluorescence-guided meningioma surgery.
| Autor: | Dijkstra BM; 1Departments of Neurosurgery., Nonnekens J; 2Department of Radiology and Nuclear Medicine, Department of Molecular Genetics, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands., Nagengast W; 3Gastroenterology and Hepatology., Kruijff S; 4Surgery., Meersma GJ; 5Medical Oncology, and., den Dunnen WFA; 6Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, The Netherlands; and., Kruyt FAE; 5Medical Oncology, and., Groen RJM; 1Departments of Neurosurgery. |
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| Jazyk: | angličtina |
| Zdroj: | Journal of neurosurgery [J Neurosurg] 2022 Oct 28; Vol. 138 (5), pp. 1263-1272. Date of Electronic Publication: 2022 Oct 28 (Print Publication: 2023). |
| DOI: | 10.3171/2022.9.JNS221036 |
| Abstrakt: | 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. |
| Databáze: | MEDLINE |
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