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-3[beta] (GSK-3[beta]) in the brain

• Published in: Journal of labelled compounds & radiopharmaceuticals 2016-06, Vol.59 (8), p.317
• Main Authors: Ono, Masahiro, Kitada, Ayane, Watanabe, Hiroyuki, Miyazaki, Anna, Kimura, Hiroyuki, Saji, Hideo
• Format: Article
• Language: eng ; fre ; ger
• Subjects: Kinases
• ISSN: 0362-4803; 1099-1344
• DOI: 10.1002/jlcr.3404

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-3[beta] (GSK-3[beta]). 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-3[beta] at a level similar to a known GSK-3[beta] inhibitor. Biodistribution studies with normal mice revealed that the radioiodinated compounds display sufficient uptake into (1.8%ID/g at 10min postinjection) and clearance from the brain (1.0%ID/g at 60min 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-3[beta].