Proceedings of the World Molecular Imaging Congress 2020, October 7-9, 2020: General Abstracts

2022 Molecular Imaging and Biology  
The epidermal growth factor receptor (EGFR) is a biomarker heterogeneously expressed in high-grade gliomas (HGGs). Administered systemically, nearinfrared fluorescent dye-labeled antibody targeting EGFR may be able to detect HGGs expressing modest amount of EGFR and serve as an image-guided surgical probe. Objective: To assess the feasibility of imaging HGGs using panitumumab-IRDye800 (pan800) in mice bearing orthotopic HGG xenografts with modest EGFR expression, and characterize EGFR protein
more » ... pression levels in human HGG tissues. Methods: Tumor mice were imaged in vivo after systemic pan800 injection to assess its tumor-specific uptake macroscopically over 14 days, and microscopically ex vivo. EGFR immunohistochemical staining of tumor specimens from 35 HGG patients during 2006-2019 was scored by pathologists and expression levels were compared to that of mouse xenografts and subsequently stratified to identify clinical characteristics that may be predictive of EGFR expression. Results: In HGG xenografts, intratumoral distribution of pan800 correlated with the EGFR expression and the fluorescence signal. Fluorescence signal distinguished tumor cells with 90% specificity and 82.5% sensitivity. Target-to-background ratios maximized at 14 hours post pan800 infusion and reached 19.5 in vivo and 7.6 ex vivo, respectively. Equivalent or higher EGFR protein expression compared to the mouse xenografts was present in 77.1% HGG patients. Age, combined with IDH-wildtype cerebral tumor, was predictive of positive EGFR protein expression in patients. Conclusion: Tumor specific uptake of pan800 provided remarkable contrast and a flexible imaging window for fluorescence-guided identification of HGGs despite modest EGFR expression. Targeted imaging and therapeutic attempts could benefit a significant HGG population.
doi:10.1007/s11307-021-01691-0 pmid:34982363 pmcid:PMC8725637 fatcat:ipn7hwekzzh6nbsk6dr2mzuhhm