肿瘤中外周型苯二氮䓬受体的成像：N-苄基-N-[(11)C]甲基-2-(7-甲基-8-氧代-2-苯基-7,8-二氢-9H-嘌呤-9-基)乙酰胺的体外结合及体内生物分布

Imaging of peripheral-type benzodiazepine receptor in tumor: in vitro binding and in vivo biodistribution of N-benzyl-N-[(11)C]methyl-2-(7-methyl-8-oxo-2-phenyl-7,8-dihydro-9H-purin-9-yl)acetamide.

作者信息

Yamasaki Tomoteru, Kumata Katsushi, Yanamoto Kazuhiko, Hatori Akiko, Takei Makoto, Nakamura Yukio, Koike Sachiko, Ando Koichi, Suzuki Kazutoshi, Zhang Ming-Rong

机构信息

Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555, Japan.

出版信息

Nucl Med Biol. 2009 Oct;36(7):801-9. doi: 10.1016/j.nucmedbio.2009.05.002. Epub 2009 Jul 9.

DOI:10.1016/j.nucmedbio.2009.05.002

PMID:19720292

Abstract

INTRODUCTION

The aim of this study was to evaluate N-benzyl-N-[(11)C]methyl-2-(7-methyl-8-oxo-2-phenyl-7,8-dihydro-9H-purin-9-yl)acetamide ([(11)C]DAC) as a novel peripheral-type benzodiazepine receptor (PBR) ligand for tumor imaging.

METHODS

[(11)C]DAC was synthesized by the reaction of a desmethyl precursor with [(11)C]CH(3)I. In vitro uptake of [(11)C]DAC was examined in PBR-expressing C6 glioma and intact murine fibrosarcoma (NFSa) cells. In vivo distribution of [(11)C]DAC was determined using NFSa-bearing mice and small-animal positron emission tomography (PET).

RESULTS

[(11)C]DAC showed specific binding to PBR in C6 glioma cells, a standard cell line with high PBR expression. Specific binding of [(11)C]DAC was also confirmed in NFSa cells, a target tumor cell line in this study. Results of PET experiments using NFSa-bearing mice, showed that [(11)C]DAC was taken up specifically into the tumor, and pretreatment with PK11195 abolished the uptake.

CONCLUSIONS

[(11)C]DAC was taken up into PBR-expressing NFSa. [(11)C]DAC is a promising PET ligand that can be used for imaging PBR in tumor-bearing mice.

摘要

引言

本研究旨在评估N-苄基-N-[(11)C]甲基-2-(7-甲基-8-氧代-2-苯基-7,8-二氢-9H-嘌呤-9-基)乙酰胺([(11)C]DAC)作为一种新型外周型苯二氮䓬受体(PBR)配体用于肿瘤成像。

方法

[(11)C]DAC通过去甲基前体与[(11)C]CH(3)I反应合成。在表达PBR的C6胶质瘤细胞和完整的小鼠纤维肉瘤(NFSa)细胞中检测[(11)C]DAC的体外摄取。使用荷NFSa小鼠和小动物正电子发射断层扫描(PET)确定[(11)C]DAC的体内分布。

结果

[(11)C]DAC在C6胶质瘤细胞中显示出与PBR的特异性结合，C6胶质瘤细胞是一种PBR高表达的标准细胞系。[(11)C]DAC在NFSa细胞中的特异性结合也得到证实，NFSa细胞是本研究中的靶肿瘤细胞系。使用荷NFSa小鼠的PET实验结果表明，[(11)C]DAC被特异性摄取到肿瘤中，用PK11195预处理可消除摄取。