Characterization of AZD4694, a novel fluorinated Abeta plaque neuroimaging PET radioligand.

Positron emission tomography (PET) radioligands that bind selectively to beta-amyloid plaques (Abeta) are promising imaging tools aimed at supporting the diagnosis of Alzheimer's disease and the evaluation of new drugs aiming to modify amyloid plaque load. For extended clinical use, there is a particular need for PET tracers labeled with fluorine-18, a radionuclide with 110 min half-life allowing for central synthesis followed by wide distribution. The development of fluorinated radioligands is, however, challenging because of the lipophilic nature of aromatic fluorine, rendering fluorinated ligands more prone to have high non-specific white matter binding.

Synthesis and evaluation of 2-pyridylbenzothiazole, 2-pyridylbenzoxazole and 2-pyridylbenzofuran derivatives as 11C-PET imaging agents for beta-amyloid plaques.

The syntheses and SAR of new series of beta-amyloid binding agents are reported. The effort to optimize signal-to-background ratios for these ligands are described. Compounds 8, 21 and 30 displayed desirable lipophilicity and pharmacokinetic properties.

AZD2184: a radioligand for sensitive detection of beta-amyloid deposits.

The presence of beta-amyloid plaques in brain is a hallmark of Alzheimer's disease (AD) and serves as a biomarker for confirmation of diagnosis postmortem. Positron emission tomography (PET) radioligands such as Pittsburgh compound B ([(11)C]-2-(3-fluoro-4-methylamino-phenyl)-benzothiazol-6-ol) (PIB) binds selectively to beta-amyloid and are promising new tools supporting the clinical diagnoses of AD. In addition, such methodology may be useful for evaluation of new drugs aiming at reduction of amyloid plaque load.

Localization of neuropeptide Y receptor Y5 mRNA in the guinea pig brain by in situ hybridization.

Neuropeptide Y (NPY) has prominent stimulatory effects on food intake in virtually all animals that have been studied. In mammals, the effect is primarily mediated by receptors Y1 and Y5, which seem to contribute to different aspects of feeding behavior in guinea pigs and rats/mice. Interestingly, differences in receptor distribution among mammalian species have been reported.