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-[123I]iodonicotinamide ([123I]ETB) and evaluated
it as an imaging tracer for single-photon emission computed tomography
(SPECT) imaging of the EphA2 receptor. [123I]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 (IC50: ETB, 90.2 ± 18.9 nM). A cell-binding assay demonstrated
that [125I]ETB binds specifically to the EphA2 receptor.
The ex vivo biodistribution study of [125I]ETB in U87MG tumor-bearing mice also revealed tumor uptake (2.2%
ID/g at 240 min). In addition, [123I]ETB uptake in tumors
was visualized via SPECT/CT imaging. On the basis of the above, [123I]ETB can be considered a potential SPECT imaging tracer
for the EphA2 receptor.
Erythropoietin-producing hepatocellular receptor A2 (EphA2) is overexpressed in cancer cells and causes abnormal cell proliferation. Therefore, it has attracted attention as a target for diagnostic agents. In this study, the EphA2-230-1 monoclonal antibody (EphA2-230-1) was labeled with [ 111 In]In and evaluated as an imaging tracer for single-photon emission computed tomography (SPECT) of EphA2. EphA2-230-1 was conjugated with 2-(4-isothiocyanatobenzyl)-diethylenetriaminepentaacetic acid (p-SCN-BnDTPA) and then labeled with [ 111 In]In. [ 111 In]In-BnDTPA-EphA2-230-1 was evaluated in cell-binding, biodistribution, and SPECT/computed tomography (CT) studies. The cellular uptake ratio of [ 111 In]In-BnDTPA-EphA2-230-1 was 14.0 ± 2.1%/mg protein at 4 h in the cell-binding study. In the biodistribution study, a high uptake of [ 111 In]In-BnDTPA-EphA2-230-1 was observed in tumor tissue (14.6 ± 3.2% injected dose/g at 72 h). The superior accumulation of [ 111 In]In-BnDTPA-EphA2-230-1 in tumors was also confirmed using SPECT/CT. Therefore, [ 111 In]In-BnDTPA-EphA2-230-1 has potential as a SPECT imaging tracer for EphA2.
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