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

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