Taiki Shigeno1, Takashi Kozaka1,2, Yoji Kitamura1,2, Kazuma Ogawa2, Junichi Taki3, Seigo Kinuya1,3, Kazuhiro Shiba4,5. 1. Division of Tracer Kinetics, Advanced Science Research Center, Kanazawa, Ishikawa, Japan. 2. Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa , Ishikawa, Japan. 3. Department of Nuclear Medicine, Kanazawa University Hospital, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8640, Japan. 4. Division of Tracer Kinetics, Advanced Science Research Center, Kanazawa, Ishikawa, Japan. shiba@med.kanazawa-u.ac.jp. 5. Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa , Ishikawa, Japan. shiba@med.kanazawa-u.ac.jp.
Abstract
INTRODUCTION: We investigated the characteristics of radio-iodinated 2-[4-(2-iodophenyl)piperidino]cyclopentanol (OI5V) as a single photon emission computed tomography (SPECT) ligand for mapping sigma-1 receptor (σ-1R), which plays an important role in stress remission in many organs. METHODS: OI5V was synthesized from o-bromobenzaldehyde in three steps. OI5V was evaluated for its affinity to VAChT, σ-1 and σ-2 receptor by in vitro competitive binding assays using rat tissues and radioligands, [3H]vesamicol, ( +)-[3H]pentazocine and [3H]DTG, respectively. [125/123I]OI5V was prepared from o-trimethylstannyl-cyclopentanevesamicol (OT5V) by the iododestannylation reaction under no-carrier-added conditions. In vivo biodistribution study of [125I]OI5V in blood, brain regions and major organs of rats was performed at 2, 10, 30 and 60 min post-injection. In vivo blocking study and ex vivo autoradiography were performed to assess the binding selectivity of [125I]OI5V for σ-1 receptor. SPECT-CT imaging study was performed using [123I]OI5V. RESULTS: OI5V demonstrated high selective binding affinity for σ-1R in vitro. In the biodistribution study, the blood-brain barrier (BBB) permeability of [125I]OI5V was high and the accumulation of [125I]OI5V in the rat cortex at 2 min post-injection exceeded 2.00%ID/g. In the in vivo blocking study, the accumulation of [125I]OI5V in the brain was significantly blocked by co-administration of 0.5 μmol of SA4503 and 1.0 μmol of pentazocine. Ex vivo autoradiography revealed that the regional brain accumulation of [125I]OI5V was similar to σ-1R-rich regions of the rat brain. SPECT images of [123I]OI5V in the rat brain reflected the distribution of sigma receptors in the brain. CONCLUSIONS: This study confirmed that [125/123I]OI5V selectively binds σ-1R in the rat brain in vivo. [123I]OI5V was suggested to be useful as a σ-1R ligand for SPECT.
INTRODUCTION: We investigated the characteristics of radio-iodinated 2-[4-(2-iodophenyl)piperidino]cyclopentanol (OI5V) as a single photon emission computed tomography (SPECT) ligand for mapping sigma-1 receptor (σ-1R), which plays an important role in stress remission in many organs. METHODS:OI5V was synthesized from o-bromobenzaldehyde in three steps. OI5V was evaluated for its affinity to VAChT, σ-1 and σ-2 receptor by in vitro competitive binding assays using rat tissues and radioligands, [3H]vesamicol, ( +)-[3H]pentazocine and [3H]DTG, respectively. [125/123I]OI5V was prepared from o-trimethylstannyl-cyclopentanevesamicol (OT5V) by the iododestannylation reaction under no-carrier-added conditions. In vivo biodistribution study of [125I]OI5V in blood, brain regions and major organs of rats was performed at 2, 10, 30 and 60 min post-injection. In vivo blocking study and ex vivo autoradiography were performed to assess the binding selectivity of [125I]OI5V for σ-1 receptor. SPECT-CT imaging study was performed using [123I]OI5V. RESULTS:OI5V demonstrated high selective binding affinity for σ-1R in vitro. In the biodistribution study, the blood-brain barrier (BBB) permeability of [125I]OI5V was high and the accumulation of [125I]OI5V in the rat cortex at 2 min post-injection exceeded 2.00%ID/g. In the in vivo blocking study, the accumulation of [125I]OI5V in the brain was significantly blocked by co-administration of 0.5 μmol of SA4503 and 1.0 μmol of pentazocine. Ex vivo autoradiography revealed that the regional brain accumulation of [125I]OI5V was similar to σ-1R-rich regions of the rat brain. SPECT images of [123I]OI5V in the rat brain reflected the distribution of sigma receptors in the brain. CONCLUSIONS: This study confirmed that [125/123I]OI5V selectively binds σ-1R in the rat brain in vivo. [123I]OI5V was suggested to be useful as a σ-1R ligand for SPECT.