EGFR-targeted intraoperative fluorescence imaging detects high-grade glioma with panitumumab-IRDye800 in a phase 1 clinical trial.

Abstract

Rationale: First-line therapy for high-grade gliomas (HGGs) includes maximal safe surgical resection. The extent of resection predicts overall survival, but current neuroimaging approaches lack tumor specificity. The epidermal growth factor receptor (EGFR) is a highly expressed HGG biomarker. We evaluated the safety and feasibility of an anti-EGFR antibody, panitumuab-IRDye800, at subtherapeutic doses as an imaging agent for HGG. Methods: Eleven patients with contrast-enhancing HGGs were systemically infused with panitumumab-IRDye800 at a low (50 mg) or high (100 mg) dose 1-5 days before surgery. Near-infrared fluorescence imaging was performed intraoperatively and ex vivo, to identify the optimal tumor-to-background ratio by comparing mean fluorescence intensities of tumor and histologically uninvolved tissue. Fluorescence was correlated with preoperative T1 contrast, tumor size, EGFR expression and other biomarkers. Results: No adverse events were attributed to panitumumab-IRDye800. Tumor fragments as small as 5 mg could be detected ex vivo and detection threshold was dose dependent. In tissue sections, panitumumab-IRDye800 was highly sensitive (95%) and specific (96%) for pathology confirmed tumor containing tissue. Cellular delivery of panitumumab-IRDye800 was correlated to EGFR overexpression and compromised blood-brain barrier in HGG, while normal brain tissue showed minimal fluorescence. Intraoperative fluorescence improved optical contrast in tumor tissue within and beyond the T1 contrast-enhancing margin, with contrast-to-noise ratios of 9.5 ± 2.1 and 3.6 ± 1.1, respectively. Conclusions: Panitumumab-IRDye800 provided excellent tumor contrast and was safe at both doses. Smaller fragments of tumor could be detected at the 100 mg dose and thus more suitable for intraoperative imaging.

• Authors: Quan Zhou, Nynke S van den Berg, Eben L Rosenthal, Michael Iv, Michael Zhang, Johana C M Vega Leonel, Shannon Walters, Naoki Nishio, Monica Granucci, Roan Raymundo, Grace Yi, Hannes Vogel, Romain Cayrol, Yu-Jin Lee, Guolan Lu, Marisa Hom, Wenying Kang, Melanie Hayden Gephart, Larry Recht, Seema Nagpal, Reena Thomas, Chirag Patel, Gerald A Grant, Gordon Li
• Journal: Theranostics (Theranostics) Vol. 11 Issue 15 Pg. 7130-7143 ( 2021) ISSN: 1838-7640 [Electronic] Australia
• PMID: 34158840 (Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © The author(s).

Chemical References

• IRDye800
• Indoles
• Neoplasm Proteins
• Panitumumab
• EGFR protein, human
• ErbB Receptors

Topics

• Adult
• Aged
• Brain Neoplasms (diagnostic imaging, metabolism, surgery)
• Disease-Free Survival
• Drug Delivery Systems
• ErbB Receptors (metabolism)
• Female
• Glioma (diagnostic imaging, metabolism, surgery)
• Humans
• Indoles (administration & dosage)
• Intraoperative Care
• Male
• Middle Aged
• Neoplasm Proteins (metabolism)
• Optical Imaging
• Panitumumab (administration & dosage)
• Survival Rate