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000828052 1001_ $$0P:(DE-Juel1)131839$$aPissarek, Margit$$b0$$eCorresponding author$$ufzj
000828052 245__ $$aSmall Molecule-Assisted PET: Approaches to Imaging of Conformational Diseases of the Brain
000828052 260__ $$aIrvine, CA$$bScientific Research Publ.$$c2017
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000828052 520__ $$aPET (positron emission tomography) in vivo imaging of cerebral conformationaldiseases is essentially based on non-peptide small molecule ligands usedto detect early alterations in peptide secondary structures and subsequent accumulationof aberrant oligomers and protein deposits involved in progressiveneurodegeneration, cognitive and movement disorders. In this article, anoverview is given about tracers currently available and lead structures of potentialPET probes for detection of ß-amyloid (Aß), tau protein, α-synuclein,constitutive (PrPc) and infectious isoforms (PrPsc) of prions (proteinaceousinfectious particles) as imaging targets. Whereas the styrylpyridine derivativeflorbetapir, approved for clinical applications, the stilbene derivative florbetabenand the benzoxazole derivative BF227 show high affinity binding to Aß,preclinical investigations promise improved pharmacokinetics for benzoimidazothiazoles,aryloxazoles and benzofuran derivatives. Tau protein imagingbased clinically, presently, on the pyridine-pyridoindole T807 has got new incentivesfollowing identification of a series of pyrrolopyridine quinolines andpharmacokinetic improvements of fluoropropoxy quinolines including for instanceTHK-5351. The pyridine isoquinoline MK6240 is involved now inclinical trials. Most forward-looking efforts apply to small molecule ligands ofα-synuclein, which are expected to permit a breakthrough in differential diagnosticsof Parkinson-related dementia and Lewy body diseases. However, atthe moment the proposed lead structures are in affinity and blood brain barrierdelivery properties below the possibilities of Aß and tau protein ligands.This is the case also for potential tracers of prion proteins.
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