RESUMO
A series of novel TSPO ligands based on the tetracyclic class of translocator protein (TSPO) ligands first described by Okubo et al. was synthesised and evaluated as potential positron emitting tomography (PET) ligands for imaging TPSO in vivo. Fluorine-18 labelling of the molecules was achieved using direct radiolabelling or synthon based labelling approaches. Several of the ligands prepared have promising profiles as potential TSPO PET imaging ligands.
Assuntos
Tomografia por Emissão de Pósitrons/métodos , Receptores de GABA/análise , Receptores de GABA/metabolismo , Animais , Radioisótopos de Flúor/química , Marcação por Isótopo/métodos , Ligantes , Transporte Proteico , Ratos , Receptores de GABA/química , Relação Estrutura-AtividadeRESUMO
A series of novel ligands based on the diaryl anilide (DAA) class of translocator protein (TSPO) ligands was synthesised and evaluated as potential positron emitting tomography (PET) ligands for imaging TPSO in vivo. Fluorine-18 labelling of the molecules was achieved using direct radiolabelling or synthon based labelling approaches. Several of the ligands prepared have promising profiles as potential TSPO PET imaging ligands and will be evaluated further as potential clinical imaging agents.
Assuntos
Anilidas/química , Anilidas/metabolismo , Proteínas de Transporte/análise , Tomografia por Emissão de Pósitrons/métodos , Receptores de GABA-A/análise , Animais , Encéfalo/metabolismo , Proteínas de Transporte/química , Proteínas de Transporte/metabolismo , Radioisótopos de Flúor , Coração , Ligantes , Ratos , Ratos Wistar , Receptores de GABA-A/química , Receptores de GABA-A/metabolismo , Relação Estrutura-Atividade , Distribuição TecidualRESUMO
A series of tricyclic compounds have been synthesised and evaluated in vitro for affinity against Translocator protein 18 kDa (TSPO) and for preferred imaging properties. The most promising of the compounds were radiolabelled and evaluated in vivo to determine biodistribution and specificity for high expressing TSPO regions. Metabolite profiling in brain and plasma was also investigated. Evaluation in an autoradiography model of neuroinflammation was also carried out for the best compound, 12a ([(18)F]GE-180).