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

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.