Elsevier

Neoplasia

Volume 15, Issue 12, December 2013, Pages 1347-1353
Neoplasia

Quantitative Analysis of [11C]-Erlotinib PET Demonstrates Specific Binding for Activating Mutations of the EGFR Kinase Domain1

https://doi.org/10.1593/neo.131666Get rights and content
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Abstract

Activating mutations of the epidermal growth factor receptor (EGFR) occur in multiple tumor types, including non-small cell lung cancer (NSCLC) and malignant glioma, and have become targets for therapeutic intervention. The determination of EGFR mutation status using a noninvasive, molecular imaging approach has the potential for clinical utility. In this study, we investigated [11C]-erlotinib positron emission tomography (PET) imaging as a tool to identify activating mutations of EGFR in both glioma and NSCLC xenografts. Radiotracer specific binding was determined for high and low specific activity (SA) [11C]-erlotinib PET scans in mice bearing synchronous human cancer xenografts with different EGFR expression profiles (PC9, HCC827, U87, U87 ΔEGFR, and SW620). Although xenograft immunohistochemistry demonstrated constitutive EGFR phosphorylation, PET scan analysis using the Simplified Reference Tissue Model showed that only kinase domain mutant NSCLC (HCC827 and PC9) had significantly greater binding potentials in high versus low SA scans. Xenografts with undetectable EGFR expression (SW620), possessing wild-type EGFR (U87), and expressing an activating extracellular domain mutation (U87 ΔEGFR) were indistinguishable under both high and low SA scan conditions. The results suggest that [11C]-erlotinib is a promising radiotracer that could provide a novel clinical methodology for assessing EGFR and erlotinib interactions in patients with tumors that harbor EGFR-activating kinase domain mutations.

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1

This work was supported by a grant from the Yale Clinical Center for Investigation Scholar Award (UL1RR024139/KL2RR024138) to J.N.C., the Kalimeris fund, and support from the Yale PET Center. J.R.P. is supported by the National Science Foundation Graduate Research Fellowship under grant DGE-1122492. Any opinion, findings, and conclusions or recommendations expressed in this material are those of the authors(s) and do not necessarily reflect the views of the National Science Foundation.