Affibody-Based PET Imaging to Guide EGFR-Targeted Cancer Therapy in Head and Neck Squamous Cell Cancer Models

Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine
Thomas A BurleyGabriela Kramer-Marek

Abstract

In head and neck squamous cell cancer, the human epidermal growth factor receptor 1 (EGFR) is the dominant signaling molecule among all members of the family. So far, cetuximab is the only approved anti-EGFR monoclonal antibody used for the treatment of head and neck squamous cell cancer, but despite the benefits of adding it to standard treatment regimens, attempts to define a predictive biomarker to stratify patients for cetuximab treatment have been unsuccessful. We hypothesized that imaging with EGFR-specific radioligands may facilitate noninvasive measurement of EGFR expression across the entire tumor burden and allow for dynamic monitoring of cetuximab-mediated changes in receptor expression. Methods: EGFR-specific Affibody molecule (ZEGFR:03115) was radiolabeled with 89Zr and 18F. The radioligands were characterized in vitro and in mice bearing subcutaneous tumors with varying levels of EGFR expression. The protein dose for imaging studies was assessed by injecting 89Zr-deferoxamine-ZEGFR:03115 (2.4-3.6 MBq, 2 μg) either together with or 30 min after increasing amounts of unlabeled ZEGFR:03115 (1, 5, 10, 15, and 20 μg). PET images were acquired at 3, 24, and 48 h after injection, and the image quantification data were co...Continue Reading

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Citations

Jun 21, 2020·International Journal of Molecular Sciences·Joon-Kee YoonSu-Jin Lee
Apr 3, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Chiara Da PieveGabriela Kramer-Marek
Mar 15, 2020·Cancers·Vladimir Tolmachev, Anna Orlova
May 1, 2021·International Journal of Molecular Sciences·Sara S RinneVladimir Tolmachev
Mar 24, 2020·Chemical Reviews·Weijun WeiWeibo Cai

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Methods Mentioned

BETA
xenografts
xenograft
saturation binding
flow cytometry
confocal microscopy
saturation assay

Software Mentioned

ImageJ
GraphPad Prism
ImageQuant TL
Zen
PMOD
FlowJo

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