3-(Benzyloxy)-1-(5-[18F]fluoropentyl)-5-nitro-1H-indazole: a PET radiotracer to measure acetylcholinesterase in brain.
Future Med Chem
; 9(10): 983-994, 2017 06.
Article
em En
| MEDLINE
| ID: mdl-28632402
ABSTRACT
AIM:
Noninvasive studies of the acetylcholinesterase (AChE) level in Alzheimer's disease (AD) patients can contribute to a better understanding of the disease and its therapeutic. We propose 3-(benzyloxy)-1-(5-[18F]fluoropentyl)-5-nitro-1H-indazole, [18F]-IND1, structurally related to the AChE-inhibitor CP126,998, as a new positron emission tomography-radiotracer. EXPERIMENTAL Radiosynthesis, with 18F, stability, lipophilicity and protein binding of [18F]-IND1 were studied. In vivo behavior, in normal mice and on AD mice models, were also analyzed.RESULTS:
[18F]-IND1 was obtained in good radiochemical yield, was stable for at least 2 h in different conditions, and had adequate lipophilicity for blood-brain barrier penetration. Biodistribution studies, in normal mice, showed that [18F]-IND1 was retained in the brain after 1 h. In vivo tacrine-blocking experiments indicated this uptake could be specifically due to AChE interaction. Studies in transgenic AD mice showed differential, compared with normal mice, binding in many brain regions.CONCLUSION:
[18F]-IND1 can be used to detect AChE changes in AD patients.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Acetilcolinesterase
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Encéfalo
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Tomografia por Emissão de Pósitrons
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Doença de Alzheimer
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Indazóis
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Future Med Chem
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Uruguai