Synthesis, in vitro and in vivo evaluation of [11C]MMTP: a potential PET ligand for mGluR1 receptors.
Bioorg Med Chem Lett
; 20(12): 3499-501, 2010 Jun 15.
Article
em En
| MEDLINE
| ID: mdl-20494576
ABSTRACT
Synthesis, in vitro and in vivo evaluation of [O-methyl-(11)C]dimethylamino-3(4-methoxyphenyl)-3H-pyrido[3',2'4,5]thieno[3,2-d]pyrimidin-4-one (1), a potential imaging agent for mGluR1 receptors using PET are described. Synthesis of the corresponding desmethyl precursor 2 was achieved by demethylation of the methoxyphenyl compound 1 in 90% yield. Methylation using [(11)C]MeOTf in presence of NaOH afforded [(11)C]1 in 30% yield (EOS) with >99% chemical and radiochemical purities and with a specific activity of 3-5Ci/micromol (n=6). The total synthesis time was 30min from EOB. The radiotracer selectively labeled mGluR1 receptors in slide-mounted sections of postmortem human brain containing cerebellum, hippocampus, prefrontal cortex and striatum as demonstrated by in vitro autoradiography using phosphor-imaging. PET studies in anesthetized baboon show that [(11)C]1 penetrates the BBB and accumulates in cerebellum, a region reported to have higher expression of mGluR1. These findings suggest [(11)C]1 is a promising PET radiotracer candidate for mGluR1.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirimidinonas
/
Receptores de Glutamato Metabotrópico
/
Compostos Radiofarmacêuticos
/
Tomografia por Emissão de Pósitrons
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Estados Unidos