Theranostics 2021; 11(15):7130-7143. doi:10.7150/thno.60582 This issue Cite

Research Paper

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

Quan Zhou1,2✉, Nynke S. van den Berg2, Eben L. Rosenthal2,3, Michael Iv4, Michael Zhang1, Johana C. M. Vega Leonel1, Shannon Walters4, Naoki Nishio2, Monica Granucci5, Roan Raymundo2,5, Grace Yi2,5, Hannes Vogel6, Romain Cayrol6, Yu-Jin Lee2, Guolan Lu2, Marisa Hom2, Wenying Kang2, Melanie Hayden Gephart1, Larry Recht7, Seema Nagpal7, Reena Thomas7, Chirag Patel7, Gerald A. Grant1, Gordon Li1

1. Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA.
2. Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA.
3. Stanford Cancer Center, Stanford University, Stanford, CA, USA.
4. Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA.
5. Cancer Clinical Trials Office, Stanford University School of Medicine, Stanford, CA, USA.
6. Department of Neuropathology, Stanford University School of Medicine, Stanford, CA, USA.
7. Department of Neurology, Stanford University School of Medicine, Stanford, CA, USA.

Citation:
Zhou Q, van den Berg NS, Rosenthal EL, Iv M, Zhang M, Vega Leonel JCM, Walters S, Nishio N, Granucci M, Raymundo R, Yi G, Vogel H, Cayrol R, Lee YJ, Lu G, Hom M, Kang W, Hayden Gephart M, Recht L, Nagpal S, Thomas R, Patel C, Grant GA, Li G. EGFR-targeted intraoperative fluorescence imaging detects high-grade glioma with panitumumab-IRDye800 in a phase 1 clinical trial. Theranostics 2021; 11(15):7130-7143. doi:10.7150/thno.60582. https://www.thno.org/v11p7130.htm
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Abstract

Graphic 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.

Keywords: High-grade glioma, epidermal growth factor receptor, panitumumab-IRDye800, fluorescence imaging, phase 1


Citation styles

APA
Zhou, Q., van den Berg, N.S., Rosenthal, E.L., Iv, M., Zhang, M., Vega Leonel, J.C.M., Walters, S., Nishio, N., Granucci, M., Raymundo, R., Yi, G., Vogel, H., Cayrol, R., Lee, Y.J., Lu, G., Hom, M., Kang, W., Hayden Gephart, M., Recht, L., Nagpal, S., Thomas, R., Patel, C., Grant, G.A., Li, G. (2021). EGFR-targeted intraoperative fluorescence imaging detects high-grade glioma with panitumumab-IRDye800 in a phase 1 clinical trial. Theranostics, 11(15), 7130-7143. https://doi.org/10.7150/thno.60582.

ACS
Zhou, Q.; van den Berg, N.S.; Rosenthal, E.L.; Iv, M.; Zhang, M.; Vega Leonel, J.C.M.; Walters, S.; Nishio, N.; Granucci, M.; Raymundo, R.; Yi, G.; Vogel, H.; Cayrol, R.; Lee, Y.J.; Lu, G.; Hom, M.; Kang, W.; Hayden Gephart, M.; Recht, L.; Nagpal, S.; Thomas, R.; Patel, C.; Grant, G.A.; Li, G. EGFR-targeted intraoperative fluorescence imaging detects high-grade glioma with panitumumab-IRDye800 in a phase 1 clinical trial. Theranostics 2021, 11 (15), 7130-7143. DOI: 10.7150/thno.60582.

NLM
Zhou Q, van den Berg NS, Rosenthal EL, Iv M, Zhang M, Vega Leonel JCM, Walters S, Nishio N, Granucci M, Raymundo R, Yi G, Vogel H, Cayrol R, Lee YJ, Lu G, Hom M, Kang W, Hayden Gephart M, Recht L, Nagpal S, Thomas R, Patel C, Grant GA, Li G. EGFR-targeted intraoperative fluorescence imaging detects high-grade glioma with panitumumab-IRDye800 in a phase 1 clinical trial. Theranostics 2021; 11(15):7130-7143. doi:10.7150/thno.60582. https://www.thno.org/v11p7130.htm

CSE
Zhou Q, van den Berg NS, Rosenthal EL, Iv M, Zhang M, Vega Leonel JCM, Walters S, Nishio N, Granucci M, Raymundo R, Yi G, Vogel H, Cayrol R, Lee YJ, Lu G, Hom M, Kang W, Hayden Gephart M, Recht L, Nagpal S, Thomas R, Patel C, Grant GA, Li G. 2021. EGFR-targeted intraoperative fluorescence imaging detects high-grade glioma with panitumumab-IRDye800 in a phase 1 clinical trial. Theranostics. 11(15):7130-7143.

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