Visualization of AMPA receptors in living human brain with positron emission tomography.
Nat Med
; 26(2): 281-288, 2020 02.
Article
em En
| MEDLINE
| ID: mdl-31959988
ABSTRACT
Although aberrations in the number and function of glutamate AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors are thought to underlie neuropsychiatric disorders, no methods are currently available for visualizing AMPA receptors in the living human brain. Here we developed a positron emission tomography (PET) tracer for AMPA receptors. A derivative of 4-[2-(phenylsulfonylamino)ethylthio]-2,6-difluoro-phenoxyacetamide radiolabeled with 11C ([11C]K-2) showed specific binding to AMPA receptors. Our clinical trial with healthy human participants confirmed reversible binding of [11C]K-2 in the brain according to Logan graphical analysis (UMIN000020975; study design:
non-randomized, single arm; primaryoutcome:
dynamics and distribution volumes of [11C]K-2 in the brain; secondaryoutcome:
adverse events of [11C]K-2 during the 4-10 d following dosing; this trial met prespecified endpoints). In an exploratory clinical study including patients with epilepsy, we detected increased [11C]K-2 uptake in the epileptogenic focus of patients with mesial temporal lobe epilepsy, which was closely correlated with the local AMPA receptor protein distribution in surgical specimens from the same individuals (UMIN000025090; studydesign:
non-randomized, single arm; primaryoutcome:
correlation between [11C]K-2 uptake measured with PET before surgery and AMPA receptor protein density examined by biochemical study after surgery; secondaryoutcome:
adverse events during the 7 d following PET scan; this trial met prespecified endpoints). Thus, [11C]K-2 is a potent PET tracer for AMPA receptors, potentially providing a tool to examine the involvement of AMPA receptors in neuropsychiatric disorders.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fenoxiacetatos
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Encéfalo
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Radioisótopos de Carbono
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Receptores de AMPA
Tipo de estudo:
Clinical_trials
Limite:
Adult
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Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Nat Med
Ano de publicação:
2020
Tipo de documento:
Article