Open AccessA Putative Single-Photon Emission CT Imaging Tracer for Erythropoietin-Producing Hepatocellular A2 Receptor
Author(s) -
Takenori Furukawa,
Hiroyuki Kimura,
Hanae Torimoto,
Yusuke Yagi,
Hidekazu Kawashima,
Kenji Arimitsu,
Hiroyuki Yasui
Publication year - 2021
Publication title -
acs medicinal chemistry letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 66
ISSN - 1948-5875
DOI - 10.1021/acsmedchemlett.1c00030
Subject(s) - eph receptor a2 , receptor tyrosine kinase , receptor , chemistry , biodistribution , in vivo , ex vivo , cancer research , medicine , in vitro , biology , biochemistry , microbiology and biotechnology
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 N -(5-((4-((4-ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)carbamoyl)-2-methylphenyl)-5-[ 123 I]iodonicotinamide ([ 123 I]ETB) and evaluated it as an imaging tracer for single-photon emission computed tomography (SPECT) imaging of the EphA2 receptor. [ 123 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 in vitro (IC 50 : ETB, 90.2 ± 18.9 nM). A cell-binding assay demonstrated that [ 125 I]ETB binds specifically to the EphA2 receptor. The ex vivo biodistribution study of [ 125 I]ETB in U87MG tumor-bearing mice also revealed tumor uptake (2.2% ID/g at 240 min). In addition, [ 123 I]ETB uptake in tumors was visualized via SPECT/CT imaging. On the basis of the above, [ 123 I]ETB can be considered a potential SPECT imaging tracer for the EphA2 receptor.