Radiosynthesis and biological evaluation of 18F-labeled 4-anilinoquinazoline derivative (18F-FEA-Erlotinib) as a potential EGFR PET agent
| Autor: | Penghui Sun, Yong-Shuai Qi, Zhiyun Du, Shun Huang, Suqing Zhao, Hubing Wu, Kongzhen Hu, Kun Zhang, Quanshi Wang, Men Wang, Yanjiang Han, Xi Zheng, Min Chen, Guiping Li |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Biodistribution medicine.drug_class Clinical Biochemistry Pharmaceutical Science Pharmacology Biochemistry Tyrosine-kinase inhibitor 03 medical and health sciences 0302 clinical medicine Gefitinib In vivo Drug Discovery medicine Epidermal growth factor receptor Erlotinib Hydrochloride Molecular Biology biology Chemistry Organic Chemistry Radiosynthesis respiratory tract diseases 030104 developmental biology 030220 oncology & carcinogenesis biology.protein Molecular Medicine Erlotinib medicine.drug |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 28:1143-1148 |
| ISSN: | 0960-894X |
| Popis: | Epidermal growth factor receptor (EGFR) has gained significant attention as a therapeutic target. Several EGFR targeting drugs (Gefitinib and Erlotinib) have been approved by US Food and Drug Administration (FDA) and have received high approval in clinical treatment. Nevertheless, the curative effect of these medicines varied in many solid tumors because of the different levels of expression and mutations of EGFR. Therefore, several PET radiotracers have been developed for the selective treatment of responsive patients who undergo PET/CT imaging for tyrosine kinase inhibitor (TKI) therapy. In this study, a novel fluorine-18 labeled 4-anilinoquinazoline based PET tracer, 1N-(3-(1-(2-18F-fluoroethyl)-1H-1,2,3-triazol-4-yl)phenyl)-6,7-bis(2-methoxyethoxy)quinazolin-4-amine (18F-FEA-Erlotinib), was synthesized and biological evaluation was performed in vitro and in vivo. 18F-FEA-Erlotinib was achieved within 50min with over 88% radiochemical yield (decay corrected RCY), an average specific activity over 50GBq/μmol, and over 99% radiochemical purity. In vitro stability study showed no decomposition of 18F-FEA-Erlotinib after incubated in PBS and FBS for 2h. Cellular uptake and efflux experiment results indicated the specific binding of 18F-FEA-Erlotinib to HCC827 cell line with EGFR exon 19 deletions. In vivo, Biodistribution studies revealed that 18F-FEA-Erlotinib exhibited rapid blood clearance both through hepatobiliary and renal excretion. The tumor uptake of 18F-FEA-Erlotinib in HepG2, HCC827, and A431 tumor xenografts, with different EGFR expression and mutations, was visualized in PET images. Our results demonstrate the feasibility of using 18F-FEA-Erlotinib as a PET tracer for screening EGFR TKIs sensitive patients. |
| Databáze: | OpenAIRE |
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