Ligand-based design of [18F]OXD-2314 for PET imaging in non-Alzheimer's disease tauopathies.
Nat Commun
; 15(1): 5109, 2024 Jun 14.
Article
em En
| MEDLINE
| ID: mdl-38877019
ABSTRACT
Positron emission tomography (PET) imaging of tau aggregation in Alzheimer's disease (AD) is helping to map and quantify the in vivo progression of AD pathology. To date, no high-affinity tau-PET radiopharmaceutical has been optimized for imaging non-AD tauopathies. Here we show the properties of analogues of a first-in-class 4R-tau lead, [18F]OXD-2115, using ligand-based design. Over 150 analogues of OXD-2115 were synthesized and screened in post-mortem brain tissue for tau affinity against [3H]OXD-2115, and in silico models were used to predict brain uptake. [18F]OXD-2314 was identified as a selective, high-affinity non-AD tau PET radiotracer with favorable brain uptake, dosimetry, and radiometabolite profiles in rats and non-human primate and is being translated for first-in-human PET studies.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Encéfalo
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Radioisótopos de Flúor
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Proteínas tau
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Compostos Radiofarmacêuticos
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Tauopatias
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Tomografia por Emissão de Pósitrons
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Doença de Alzheimer
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article