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

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

doi:10.1016/j.nucmedbio.2009.05.002

« Previous Next »Nuclear Medicine and Biology
Volume 36, Issue 7 , Pages 801-809, October 2009

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

Tomoteru Yamasaki
- Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555, Japan
Katsushi Kumata
- Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555, Japan
Kazuhiko Yanamoto
- Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555, Japan
Akiko Hatori
- Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555, Japan
Makoto Takei
- Tokyo Nuclear Service Co. Ltd., Tokyo 141-8686, Japan
Yukio Nakamura
- Tokyo Nuclear Service Co. Ltd., Tokyo 141-8686, Japan
Sachiko Koike
- Heavy-ion Radiobiology Research Group, National Institute of Radiological Sciences, Chiba 263-8555, Japan
Koichi Ando
- Heavy-ion Radiobiology Research Group, National Institute of Radiological Sciences, Chiba 263-8555, Japan
Kazutoshi Suzuki
- Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555, Japan
Ming-Rong Zhang
- Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555, Japan
- Corresponding author. Radiochemistry Section, Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555, Japan. Tel.: +81 43 206 4041; fax: +81 43 206 3261.

Received 20 February 2009; received in revised form 30 April 2009; accepted 12 May 2009. published online 10 July 2009.

Abstract

Introduction

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

Methods

[¹¹C]DAC was synthesized by the reaction of a desmethyl precursor with [¹¹C]CH₃I. In vitro uptake of [¹¹C]DAC was examined in PBR-expressing C6 glioma and intact murine fibrosarcoma (NFSa) cells. In vivo distribution of [¹¹C]DAC was determined using NFSa-bearing mice and small-animal positron emission tomography (PET).

Results

[¹¹C]DAC showed specific binding to PBR in C6 glioma cells, a standard cell line with high PBR expression. Specific binding of [¹¹C]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 [¹¹C]DAC was taken up specifically into the tumor, and pretreatment with PK11195 abolished the uptake.