Synthesis and biological evaluation of radio-iodinated benzimidazoles as SPECT imaging agents for NR2B subtype of NMDA receptor.

In this study, the benzimidazole derivatives were synthesized and evaluated as imaging agents for the NR2B subtype of NMDA receptor. Among these ligands, 2-{[4-(4-iodobenzyl)piperidin-1-yl]methyl}benzimidazol-5-ol (8) and N-{2-[4-(4-iodobenzyl)-piperidin-1-ylmethyl]benzoimidazol-5-yl}-methanesulfonamide (9) exhibited high affinity for the NR2B subunit (K(i) values; 7.28 nM for 8 and 5.75 nM for 9). In vitro autoradiography experiments demonstrated high accumulation in the forebrain regions but low in the cerebellum for both [(125)I]8 and [(125)I]9. These regional distributions of the radioligands correlated with the expression of the NR2B subunit. The in vitro binding of these ligands was inhibited by NR2B antagonist but not by other site ligands, which suggested the high selectivity of [(125)I]8 and [(125)I]9 for the NR2B subunit. In mice, the regional brain uptakes of [(125)I]8 and [(125)I]9 at 5-180 min after administration were 0.42-0.56% and 0.44-0.67% dose/g, respectively. The brain-to-blood ratio of [(125)I]8 at 180 min was reduced by 34% in the presence of non-radioactive ligands and by 59% in the presence of the NR2B ligand Ro-25,6981. These results indicated that [(125)I]8 could be partially bound to the NR2B subunit in vivo. Although the brain uptake of these benzimidazole derivatives was too low to allow for in vivo SPECT imaging, these compounds might be useful scaffolds for the development of imaging probes specific for the NMDA receptors

Non-Glycosidically Linked Pseudodisaccharides: Thioethers, Sulfoxides, Sulfones, Ethers, Selenoethers, and Their Binding to Lectins

Hydrolytically stable non-glycosidically linked tail-to-tail pseudodisaccharides are linked by a single bridging atom remote from the anomeric centre of the constituent monosaccharides. Some such pseudodisaccharides with sulfur or oxygen bridges were found to act as disaccharide mimetics in their binding to the Banana Lectin and to Concanavalin A. A versatile synthetic route to a small library of such compounds is described.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/69166/1/1951_ftp.pd

In vitro and vivo evaluation of C-11 labeled cinnamamidine as a new PET radioligand for NR2B/NMDA Receptors.

第５１回米国核医学会年会に参加してポスター発表（演題：NR2B/NMDA受容体の新規PETリガンドとしての炭素−１１標識シンナミジンのインビトロ及びインビボ評価）を行った。　今回の年会では、興奮性グルタミン酸受容体のPETリガンドに関して我々を含めて３件の報告があった。内、代謝性グルタミン酸受容体のPETリガンドの合成と評価の報告では、ラットでのインビボ特異結合が報告されインビボイメージング剤としての可能性が指摘され興味が持たれた。　癌のイメージングに関しては、血管新生でαVβ3インテグリンのリガンド、ヒポキシアではCu-ATSM及びFMISOの有用性評価、アポトーシスのイメージングのためのAnnexinV関連の報告が多く、臨床利用へむけての有用性が指摘されていた。The Society of Nuclear Medicine advancing molecular imagim