Characterization of a novel acetamidobenzoxazolone-based PET ligand for translocator protein (18 kDa) imaging of neuroinflammation in the brain.
J Neurochem
; 129(4): 712-20, 2014 May.
Article
em En
| MEDLINE
| ID: mdl-24484439
ABSTRACT
We developed the novel positron emission tomography (PET) ligand 2-[5-(4-[(11)C]methoxyphenyl)-2-oxo-1,3-benzoxazol-3(2H)-yl]-N-methyl-N-phenylacetamide ([(11)C]MBMP) for translocator protein (18 kDa, TSPO) imaging and evaluated its efficacy in ischemic rat brains. [(11)C]MBMP was synthesized by reacting desmethyl precursor (1) with [(11)C]CH3 I in radiochemical purity of ≥ 98% and specific activity of 85 ± 30 GBq/µmol (n = 18) at the end of synthesis. Biodistribution study on mice showed high accumulation of radioactivity in the TSPO-rich organs, e.g., the lungs, heart, kidneys, and adrenal glands. The metabolite analysis in mice brain homogenate showed 80.1 ± 2.7% intact [(11)C]MBMP at 60 min after injection. To determine the specific binding of [(11)C]MBMP with TSPO in the brain, in vitro autoradiography and PET studies were performed in an ischemic rat model. In vitro autoradiography indicated significantly increased binding on the ipsilateral side compared with that on the contralateral side of ischemic rat brains. This result was supported firmly by the contrast of radioactivity between the ipsilateral and contralateral sides in PET images. Displacement experiments with unlabelled MBMP or PK11195 minimized the difference in uptake between the two sides. In summary, [(11)C]MBMP is a potential PET imaging agent for TSPO and, consequently, for the up-regulation of microglia during neuroinflammation.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Benzoxazóis
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Encéfalo
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Radioisótopos de Carbono
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Isquemia Encefálica
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Receptores de GABA
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Microglia
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Compostos Radiofarmacêuticos
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Tomografia por Emissão de Pósitrons
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Acetanilidas
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Proteínas do Tecido Nervoso
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Revista:
J Neurochem
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Índia