Evaluation of EGFR-TK Expression with a 99mTc-Labeled complex bearing quinazoline pharmacophore

Abstract

Objectives: The epidermal growth factor receptor (EGFR) signaling pathway is widely recognized to play an important role in development and progression of many malignant tumors, including lung cancer. The aim of this study was to produce a useful technetium-99m (99mTc) complex for early detection and staging of EGFR-positive tumors. Methods: The authors labeled quinazoline derivative (3-iodinephenyl) quinazoline-4, 6-diamine with 99mTc using S-acetylmercaptoacetyltriglyglycinate (MAG3) conjugated to quinazoline derivative through 4-[(2-aminoethyl)amino]-4-oxobut-2-enoic acid because it is a bifunctional chelator with an average yield of 93.9% ± 2.5% and radiochemical purity of >98%. Results: In vitro studies indicate that the [99mTc]-complex13 has high stability in physiological conditions and binds the HCC 827 cells and shows HCC 827 internalization. The biodistribution of the [99mTc]-complex13 in healthy Institute of Cancer Research mice indicates the rather fast blood clearance through the hepatobiliary system. Conclusion: These preliminary results pave the road for estimating the status of EGFR and monitoring the response to EGFR tyrosine kinase inhibitors as a personalized cancer therapy regimen.