Synthesis and preliminary characterization of radioiodinated benzofuran‐3‐yl‐(indol‐3‐yl)maleimide derivatives as potential SPECT imaging probes for the detection of glycogen synthase kinase‐3β (GSK‐3β) in the brain |
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Authors: | Masahiro Ono Ayane Kitada Hiroyuki Watanabe Anna Miyazaki Hiroyuki Kimura Hideo Saji |
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Institution: | Department of Patho‐Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan |
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Abstract: | We report on the synthesis and preliminary characterization of two radioiodinated benzofuran‐3‐yl‐(indol‐3‐yl)maleimides, 3‐(benzofuran‐3‐yl)‐4‐(5‐125I]iodo‐1‐methyl‐1H‐indol‐3‐yl)‐1H‐pyrrole‐2,5‐dione (125I]5), and 3‐(5‐125I]iodo‐1‐methyl‐1H‐indol‐3‐yl)‐4‐(6‐methoxybenzofuran‐3‐yl)‐1H‐pyrrole‐2,5‐dione (125I]6), as the first potential SPECT imaging probes targeting glycogen synthase kinase‐3β (GSK‐3β). In this study, we used 125I as a surrogate of 123I because of its ease of use. The radioiodinated ligands were prepared from the corresponding tributyltin precursors through an iododestannylation reaction using hydrogen peroxide as an oxidant with a radiochemical yield of 10–30%. In vitro binding experiments suggested that both compounds show high affinity for GSK‐3β at a level similar to a known GSK‐3β inhibitor. Biodistribution studies with normal mice revealed that the radioiodinated compounds display sufficient uptake into (1.8%ID/g at 10 min postinjection) and clearance from the brain (1.0%ID/g at 60 min postinjection). These preliminary results suggest that the further optimization of radioiodinated benzofuran‐3‐yl‐(indol‐3‐yl)maleimide derivatives may facilitate the development of clinically useful SPECT imaging probes for the in vivo detection of GSK‐3β. |
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Keywords: | radiopharmaceutical I‐125 GSK‐3β SPECT radioiodination probe |
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