邻溴反式十氢萘vesamicol作为用于囊泡乙酰胆碱转运体成像的新型正电子发射断层显像（PET）配体的潜力。

The potential of o-bromo-trans-decalinvesamicol as a new PET ligand for vesicular acetylcholine transporter imaging.

作者信息

Azim Mohammad Anwar-Ul, Kozaka Takashi, Uno Izumi, Miwa Daisuke, Kitamura Yoji, Ogawa Kazuma, Makino Akira, Kiyono Yasushi, Shiba Kazuhiro

机构信息

Division of Tracer Kinetics, Advanced Science Research Center, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8640, Japan; Graduate School of Natural Science and Technology, Kanazawa University, Kakuma, 920-1192, Japan.

出版信息

Synapse. 2014 Oct;68(10):445-53. doi: 10.1002/syn.21756. Epub 2014 Jul 4.

DOI:10.1002/syn.21756

PMID:24953217

Abstract

We investigated the characteristics of the regional rat brain distribution of radio-brominated o-bromo-decalinvesamicol (OBDV) in vivo to evaluate its potential as a PET ligand for vesicular acetylcholine transporter (VAChT). In in vivo biodistribution study, the specific brain regional accumulation of [(77) Br]OBDV was revealed 30 min after intravenous injection. The specific brain regional accumulation of [(77) Br]OBDV was significantly inhibited by co-injection of (+/-)-vesamicol. In contrast, no significant inhibition of the uptake of [(77) Br]OBDV in all brain regions was observed with co-injection of (+)-pentazocine (selective σ-1 receptor agonist) and (+)-3-(3-hydroxyphenyl)-N-propylpiperidine, [(+)-3-PPP] (σ-1 and σ-2 receptor agonist) with [(77) Br]OBDV. [(77) Br]OBDV accumulation in VAChT-rich brain regions was observed in ex vivo autoradiography. These results showed that [(77) Br]OBDV selectively bound to VAChT with high affinity in rat brain in vivo. Hence, OVBDV radiolabelled with more suitable (76) Br was suggested to be a potent VAChT ligand for PET.

摘要

我们在体内研究了放射性溴代邻溴十氢化萘安贝氯铵（OBDV）在大鼠脑内的区域分布特征，以评估其作为囊泡乙酰胆碱转运体（VAChT）正电子发射断层显像（PET）配体的潜力。在体内生物分布研究中，静脉注射[(77)Br]OBDV 30分钟后，显示出其在脑内特定区域有蓄积。同时注射(+/-)-安贝氯铵可显著抑制[(77)Br]OBDV在脑内特定区域的蓄积。相比之下，同时注射(+)-喷他佐辛（选择性σ-1受体激动剂）和(+)-3-(3-羟基苯基)-N-丙基哌啶[（+）-3-PPP]（σ-1和σ-2受体激动剂）与[(77)Br]OBDV时，未观察到对[(77)Br]OBDV在所有脑区摄取的显著抑制。在离体放射自显影中观察到[(77)Br]OBDV在富含VAChT的脑区有蓄积。这些结果表明，[(77)Br]OBDV在大鼠脑内体内以高亲和力选择性地与VAChT结合。因此，用更合适的(76)Br标记的OVBDV被认为是一种用于PET的有效的VAChT配体。