Imaging of the translocator protein (18kDa) in rat brain after ischemia using [11C]DAC with ultra-high specific Activity

In the central nervous system, translocator protein
(TSPO) (18 kDa) (Papadopoulos et al., 2006), formerly
named peripheral-type benzodiazepine receptor
(PBR), is located in the microglial cells of the brain
(Braestrup et al., 1977; Stephenson et al., 1995).
Many studies have elucidated the relationship
between TSPO and neurodegenerative diseases, such
as Alzheimer's disease (Maeda et al., 2007; Yasuno
et al., 2008), and stroke-induced brain injury (Rojas
et al., 2007). To image TSPO in vivo, a number of
new ligands have been labeled with the positron emitters
11C and 18F (Chauveau et al., 2008). We have
developed [11C]DAA1106 (Zhang et al., 2003; Maeda
et al., 2004), [18F]FEDAA1106 (Zhang et al., 2004),
and [11C]AC-5216 (Zhang et al., 2007) for clinical
imaging of TSPO in the brain. We recently synthesized
and evaluated N-benzyl-N-[11C]methyl-2-(7-
methyl-8-oxo-2-phenyl-7, 8-dihydro-9H-purin-9-yl)acetamide
with a specific activity of 37–110 GBq/lmol for
the imaging of TSPO (Yanamoto et al., 2009).
The aim of this study was to synthesize N-benzyl-
N-methyl-2-(7-[11C]methyl-8-oxo-2-phenyl-7,8-dihydro-
9H-purin-9-yl)acetamide ([11C]DAC) with ultra-high
specific activity (average 4560 GBq/lmol), and to
characterize specific binding to TSPO in the rat brain
after ischemia. Using [11C]DAC of high specific activity,
we expected to acquire high uptake ratios
between the ipsilateral and contralateral sides and
higher binding potential for TSPO from autoradiographic
and PET images of infarct brains. Here, we
labeled the methyl group of purine ring of DAC to
achieve ultra-high specific activity using [11C]CH3I
that was prepared by iodination of [11C]CH4 (Noguchi
and Suzuki, 2003; Noguchi et al., 2008). We
performed comparative evaluation using [11C]DAC
with middle specific activity and low specific activity
to elucidate the effect of specific activity on the in
vitro and in vivo specific binding of [11C]DAC to
TSPO in an infarct rat brain after ischemia. In this
article we use the terms ''high SA,'' ''middle SA,'' and
''low SA'' to refer to specific activities of 3540–5580,
29–52, and 0.3–0.4 GBq/lmol, respectively.

書誌情報

Synapse

巻 64, 号 6, p. 488-493, 発行日 2010-06

ISSN

収録物識別子タイプ

ISSN

収録物識別子

0887-4476

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