Division of Tracer Kinetics, Advanced Science Research Center, Kanazawa, Ishikawa, Japan.
Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa , Ishikawa, Japan.
Ann Nucl Med. 2021 Feb;35(2):167-175. doi: 10.1007/s12149-020-01552-w. Epub 2021 Jan 8.
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.
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, [H]vesamicol, ( +)-[H]pentazocine and [H]DTG, respectively. [I]OI5V was prepared from o-trimethylstannyl-cyclopentanevesamicol (OT5V) by the iododestannylation reaction under no-carrier-added conditions. In vivo biodistribution study of [I]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 [I]OI5V for σ-1 receptor. SPECT-CT imaging study was performed using [I]OI5V.
OI5V demonstrated high selective binding affinity for σ-1R in vitro. In the biodistribution study, the blood-brain barrier (BBB) permeability of [I]OI5V was high and the accumulation of [I]OI5V in the rat cortex at 2 min post-injection exceeded 2.00%ID/g. In the in vivo blocking study, the accumulation of [I]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 [I]OI5V was similar to σ-1R-rich regions of the rat brain. SPECT images of [I]OI5V in the rat brain reflected the distribution of sigma receptors in the brain.
This study confirmed that [I]OI5V selectively binds σ-1R in the rat brain in vivo. [I]OI5V was suggested to be useful as a σ-1R ligand for SPECT.
我们研究了放射性碘标记 2-[4-(2-碘苯基)哌啶基]环戊醇（OI5V）作为单光子发射计算机断层扫描（SPECT）配体用于映射 sigma-1 受体（σ-1R）的特征，该受体在许多器官的应激缓解中发挥重要作用。
OI5V 由邻溴苯甲醛通过三步合成。通过使用大鼠组织和放射性配体 [H]vesamicol、（+）-[H]pentazocine 和 [H]DTG 的体外竞争性结合测定，评估 OI5V 对 VAChT、σ-1 和 σ-2 受体的亲和力。[I]OI5V 由邻三甲基锡基-环戊基 vesamicol（OT5V）通过无载体添加条件下的碘脱锡反应制备。在大鼠血、脑区和主要器官中的 [I]OI5V 体内分布研究在注射后 2、10、30 和 60 分钟进行。进行体内阻断研究和离体放射自显影以评估 [I]OI5V 对 σ-1 受体的结合选择性。使用 [I]OI5V 进行 SPECT-CT 成像研究。
OI5V 在体外对 σ-1R 表现出高选择性结合亲和力。在分布研究中，[I]OI5V 的血脑屏障（BBB）通透性很高，大鼠皮质中 [I]OI5V 的积累在注射后 2 分钟超过 2.00%ID/g。在体内阻断研究中，SA4503 0.5 μmol 和戊唑辛 1.0 μmol 的共同给药显著阻止了 [I]OI5V 在大脑中的积累。离体放射自显影显示，[I]OI5V 在大脑中的区域积累与大鼠大脑中富含 σ-1R 的区域相似。[I]OI5V 在大鼠大脑中的 SPECT 图像反映了大脑中 sigma 受体的分布。
这项研究证实了 [I]OI5V 在体内选择性结合大鼠大脑中的 σ-1R。[I]OI5V 有望成为 SPECT 中 σ-1R 配体的有用工具。
