Visualization of α5 subunit of GABA A /benzodiazepine receptor by [ 11 C]Ro15‐4513 using positron emission tomography
2002; Wiley; Volume: 47; Issue: 3 Linguagem: Inglês
10.1002/syn.10169
ISSN1098-2396
AutoresJun Maeda, Tetsuya Suhara, Kouichi Kawabe, Takashi Okauchi, Shigeru Obayashi, Junko Hojo, Kazutoshi Suzuki,
Tópico(s)Advanced MRI Techniques and Applications
ResumoAbstract Although [ 11 C]Ro15‐4513 and [ 11 C]flumazenil both bind to the central benzodiazepine (BZ) receptors, the distributions of the two ligands are not identical in vivo. Moreover, the in vivo pharmacological properties of [ 11 C]Ro15‐4513 have not been thoroughly examined. In the present study, we examined the pharmacological profile of [ 11 C]Ro15‐4513 binding in the monkey brain using positron emission tomography (PET). [ 11 C]Ro15‐4513 showed relatively high accumulation in the anterior cingulate cortex, hippocampus, and insular cortex, with the lowest uptake being observed in the pons. Accumulation in the cerebral cortex was significantly diminished by the BZ antagonist flumazenil (0.1 mg/kg, i.v.), but not that in the pons. Using the pons as a reference region, the specific binding of [ 11 C]Ro15‐4513 in most of the cerebral cortex including the limbic regions clearly revealed two different affinity sites. On the other hand, specific binding in the occipital cortex and cerebellum showed only a low affinity site. Zolpidem with affinity for α1, α2, and α3 subunits of GABA A /BZ receptor fully inhibited [ 11 C]Ro15‐4513 binding in the occipital cortex and cerebellum, while only about 23% of the binding was blocked in the anterior cingulate cortex. Diazepam with affinity for α1, α2, α3, and α5 subunits inhibited the binding in all brain regions. Since Ro15‐4513 has relatively high affinity for the α5 subunit in vitro, these in vivo bindings of [ 11 C]Ro15‐4513 can be interpreted as the relatively high accumulation in the fronto‐temporal limbic regions representing binding to the GABA A /BZ receptor α5 subunit. Synapse 47:200–208, 2003. © 2002 Wiley‐Liss, Inc.
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