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

• Published in: Journal of labelled compounds & radiopharmaceuticals 2016-06, Vol.59 (8), p.317-321
• Main Authors: Ono, Masahiro, Kitada, Ayane, Watanabe, Hiroyuki, Miyazaki, Anna, Kimura, Hiroyuki, Saji, Hideo
• Format: Article
• Language: English
• Subjects: Animals; Brain - diagnostic imaging; Brain - enzymology; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - metabolism; Enzyme Inhibitors - pharmacokinetics; Glycogen Synthase Kinase 3 beta - antagonists & inhibitors; Glycogen Synthase Kinase 3 beta - metabolism; GSK-3β; I-125; Iodine Radioisotopes - chemistry; Isotope Labeling; Male; Maleimides - chemical synthesis; Maleimides - chemistry; Maleimides - metabolism; Maleimides - pharmacokinetics; Mice; probe; radioiodination; radiopharmaceutical; SPECT; Tissue Distribution; Tomography, Emission-Computed, Single-Photon - methods
• 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‐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. We report on the synthesis and preliminary characterization of radioiodinated benzofuran‐3‐yl‐(indol‐3‐yl)maleimide derivatives ([125I]5 and [125I]6) as new SPECT imaging agents targeting GSK‐3β in the brain. The results in this study suggest that the further optimization of radioiodinated benzofuran‐3‐yl‐(indol‐3‐yl)maleimide derivatives may provide possibility for the development of clinically useful SPECT imaging probes for the in vivo detection of GSK‐3β.