Synthesis, in vitro and in vivo evaluation of fluorine-18 labelled FE-GW405833 as a PET tracer for type 2 cannabinoid receptor imaging.
Bioorg Med Chem
; 19(15): 4499-505, 2011 Aug 01.
Article
em En
| MEDLINE
| ID: mdl-21737287
The type 2 cannabinoid receptor (CB2R) is part of the endocannabinoid system and is expressed in tissues related to the immune system. As the CB2R has a very low brain expression in non-pathological conditions, but is upregulated in activated microglia, it is an interesting target for visualization of neuroinflammation using positron emission tomography with a suitable radiolabeled CB2R ligand. In this study, we radiolabelled a fluoroethyl derivative of GW405833, a well known CB2R partial agonist, with fluorine-18 (half-life 109.8 min) by alkylation of the phenol precursor with 1-bromo-2-[¹8F]fluoroethane. In vitro studies showed that FE-GW405833 behaved as a selective high affinity (27 nM) inverse agonist for hCB2R. [¹8F]FE-GW405833 showed moderate initial brain uptake in mice and rats, but a slow washout from brain and plasma due to retention of a radiometabolite. Specific binding of the tracer to human CB2R was demonstrated in vivo in a rat model with local CB2R overexpression in the brain. Optimized derivatives of GW405833 that are less susceptible to metabolism will need to be developed in order to provide a useful tracer for CB2R quantification with PET.
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MEDLINE
Assunto principal:
Encéfalo
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Radioisótopos de Flúor
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Morfolinas
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Receptor CB2 de Canabinoide
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Tomografia por Emissão de Pósitrons
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Indóis
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article