Preclinical properties and human in vivo assessment of 123I-ABC577 as a novel SPECT agent for imaging amyloid-ß.
Brain
; 139(Pt 1): 193-203, 2016 Jan.
Article
em En
| MEDLINE
| ID: mdl-26490333
ABSTRACT
Non-invasive imaging of amyloid-ß in the brain, a hallmark of Alzheimer's disease, may support earlier and more accurate diagnosis of the disease. In this study, we assessed the novel single photon emission computed tomography tracer (123)I-ABC577 as a potential imaging biomarker for amyloid-ß in the brain. The radio-iodinated imidazopyridine derivative (123)I-ABC577 was designed as a candidate for a novel amyloid-ß imaging agent. The binding affinity of (123)I-ABC577 for amyloid-ß was evaluated by saturation binding assay and in vitro autoradiography using post-mortem Alzheimer's disease brain tissue. Biodistribution experiments using normal rats were performed to evaluate the biokinetics of (123)I-ABC577. Furthermore, to validate (123)I-ABC577 as a biomarker for Alzheimer's disease, we performed a clinical study to compare the brain uptake of (123)I-ABC577 in three patients with Alzheimer's disease and three healthy control subjects. (123)I-ABC577 binding was quantified by use of the standardized uptake value ratio, which was calculated for the cortex using the cerebellum as a reference region. Standardized uptake value ratio images were visually scored as positive or negative. As a result, (123)I-ABC577 showed high binding affinity for amyloid-ß and desirable pharmacokinetics in the preclinical studies. In the clinical study, (123)I-ABC577 was an effective marker for discriminating patients with Alzheimer's disease from healthy control subjects based on visual images or the ratio of cortical-to-cerebellar binding. In patients with Alzheimer's disease, (123)I-ABC577 demonstrated clear retention in cortical regions known to accumulate amyloid, such as the frontal cortex, temporal cortex, and posterior cingulate. In contrast, less, more diffuse, and non-specific uptake without localization to these key regions was observed in healthy controls. At 150 min after injection, the cortical standardized uptake value ratio increased by â¼ 60% in patients with Alzheimer's disease relative to healthy control subjects. Both healthy control subjects and patients with Alzheimer's disease showed minimal (123)I-ABC577 retention in the white matter. These observations indicate that (123)I-ABC577 may be a useful single photon emission computed tomography imaging maker to identify amyloid-ß in the human brain. The availability of an amyloid-ß tracer for single photon emission computed tomography might increase the accessibility of diagnostic imaging for Alzheimer's disease.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Piridinas
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Tomografia Computadorizada de Emissão de Fóton Único
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Peptídeos beta-Amiloides
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Doença de Alzheimer
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Neuroimagem Funcional
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Imidazóis
Tipo de estudo:
Observational_studies
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Prognostic_studies
Limite:
Adult
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Aged
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Aged80
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Animals
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article