A Putative Single-Photon Emission CT Imaging Tracer for Erythropoietin-Producing Hepatocellular A2 Receptor.

ACS Med Chem Lett

Department of Analytical and Bioinorganic Chemistry, Division of Analytical and Physical Chemistry, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.

Published: August 2021

Erythropoietin-producing hepatocellular (Eph) receptors are receptor tyrosine kinases involved in cell-cell contact. The EphA2 receptor is associated with cancer proliferation and migration. Therefore, EphA2 receptor imaging has the potential for cancer diagnosis. Here, we synthesized -(5-((4-((4-ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)carbamoyl)-2-methylphenyl)-5-[I]iodonicotinamide ([I]ETB) and evaluated it as an imaging tracer for single-photon emission computed tomography (SPECT) imaging of the EphA2 receptor. [I]ETB was designed on the basis of ALW-II-41-27, an inhibitor of EphA2 receptor kinase. Nonradioactive ETB was also synthesized and has been shown to efficiently inhibit EphA2 receptor kinase activity (IC: ETB, 90.2 ± 18.9 nM). A cell-binding assay demonstrated that [I]ETB binds specifically to the EphA2 receptor. The biodistribution study of [I]ETB in U87MG tumor-bearing mice also revealed tumor uptake (2.2% ID/g at 240 min). In addition, [I]ETB uptake in tumors was visualized via SPECT/CT imaging. On the basis of the above, [I]ETB can be considered a potential SPECT imaging tracer for the EphA2 receptor.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8365995PMC
http://dx.doi.org/10.1021/acsmedchemlett.1c00030DOI Listing

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