In vivo characterization of radioiodinated (+)-2-[4-(4-iodophenyl) piperidino] cyclohexanol as a potential σ-1 receptor imaging agent

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• 作者：Nasima Akhter ; Kazuhiro Shiba ; Kazuma Ogawa ; Seigo Kinuya ; Kenichi Nakajima ; Hirofumi Mori
• 关键词：(+)-p-Iodovesamicol ; σ ; -1 receptor ; Radioligand ; Biodistribution
• 刊名：Nuclear Medicine and Biology
• 出版年：2007
• 出版时间：August 2007
• 年：2007
• 卷：34
• 期：6
• 页码：697-702
• 全文大小：451 K

文摘

In this study, the (+)-enantiomer of radioiodinated 2-[4-(4-iodophenyl)piperidino]cyclohexanol [(+)-[¹²⁵I]-p-iodovesamicol] [(+)-[¹²⁵I]pIV], which is reported to bind with high affinity to σ-1 receptors in vitro, was tested for its usefulness in imaging σ-1 receptors in the central nervous system (CNS) in vivo. In biodistribution studies, significant amounts (approximately 3 % of the injected dose) of (+)-[¹²⁵I]pIV accumulated in rat brain, and its retention was prolonged. In blocking studies, the accumulation of (+)-[¹²⁵I]pIV in the rat brain was significantly reduced by the coadministration of σ-ligands such as pentazocine (5.0 μmol), haloperidol (0.5 μmol) or SA4503 (0.5 μmol). The blocking effect of pentazocine (selective σ-1 ligand) was similar to the blocking effects of SA4503 and haloperidol [nonselective σ (σ-1 and σ-2) ligands]. Ex vivo autoradiography of the rat brain at 45 min following intravenous injection of (+)-[¹²⁵I]pIV showed high localization in brain areas rich in σ-1 receptors. Thus, the distribution of (+)-[¹²⁵I]pIV was thought to bind to σ-1 receptors in the CNS in vivo. These results indicate that radioiodinated (+)-pIV may have the potential to image σ-1 receptors in vivo.