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.
BACKGROUND
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.
Yamasaki
Tomoteru
T
Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555, Japan.
Kumata
Katsushi
K
Yanamoto
Kazuhiko
K
Hatori
Akiko
A
Takei
Makoto
M
Nakamura
Yukio
Y
Koike
Sachiko
S
Ando
Koichi
K
Suzuki
Kazutoshi
K
Zhang
Ming-Rong
MR
D000081:Acetamides / Q000737:chemistry / Q000493:pharmacokinetics*; D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism*; D007150:Immunohistochemistry; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D051379:Mice; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology; D049268:Positron-Emission Tomography; D011485:Protein Binding / Q000187:drug effects; D011687:Purines / Q000737:chemistry / Q000493:pharmacokinetics*; D011854:Radiochemistry; D051381:Rats; D018079:Receptors, GABA / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000378:metabolism*; D014018:Tissue Distribution
D000081:Acetamides; C463819:Bzrp protein, mouse; D002352:Carrier Proteins; D007546:Isoquinolines; C545830:N-benzyl-N-methyl-2-(7-methyl-8-oxo-2-phenyl-7,8-dihydro-9H-purin-9-yl)acetamide; D011687:Purines; D018079:Receptors, GABA; D011963:Receptors, GABA-A; C069997:Tspo protein, rat; C030686:acetamide; C037850:PK 11195