Synthesis and evaluation of radioiodinated phenoxyquinazoline and benzylaminoquinazoline derivatives as new EGF receptor tyrosine kinase imaging ligands for tumor diagnosis using SPECT

Annals of Nuclear Medicine
Masahiko HirataYoshiro Ohmomo

Abstract

Epidermal growth factor receptor tyrosine kinase (EGFR-TK) represents an attractive target for tumor diagnosis agents. Previously, the radioiodinated 4-(3-iodoanilino)-6,7-diethoxyquinazoline ([(125)I]m-IPQ) has been reported to possess good characteristics as a tumor imaging agent; however, it was also found to have low in vivo stability. To improve the in vivo stability, m-IPQ derivatives, 4-(3-iodophenoxy)-6,7-diethoxyquinazoline (PHY) and 4-(3-iodobenzylamino)-6,7-diethoxyquinazoline (BAY) were designed and synthesized, and the biological studies of [(125)I]PHY and [(125)I]BAY were performed to evaluate these new ligands as in vivo tumor diagnosis agents. PHY and BAY were synthesized according to previous reports. The EGFR-TK inhibitory potency of these new compounds was measured and compared to other EGFR-TK inhibitors. Radiolabeled [(125)I]PHY and [(125)I]BAY were synthesized by an iododestannylation reaction. Biodistribution studies of these radioligands were conducted in normal mice and tumor-bearing mice. Furthermore, selectivity and binding characteristics of [(125)I]PHY were analyzed by in vitro blocking studies and a binding assay. The new derivatives were found to have high inhibitory potency against EGFR-TK (PHY: ...Continue Reading

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Citations

Mar 4, 2014·Biological & Pharmaceutical Bulletin·Mitsuyoshi YoshimotoYoshiro Ohmomo
Jul 30, 2014·Nuclear Medicine and Biology·Paul SlobbeAlex J Poot
Jul 25, 2017·European Journal of Organic Chemistry·Lorenzo CavinaFloris P J T Rutjes

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