Preclinical properties and humanin vivoassessment of123I-ABC577 as a novel SPECT agent for imaging amyloid-β
| Autor: | David Alagille, John Seibyl, Olivier Barret, Yuki Okumura, Takako Onishi, Akihiro Tanaka, Yoshifumi Shirakami, Ryohei Kobayashi, Danna Jennings, Yoshifumi Maya, Gilles Tamagnan, Yoshinari Shoyama, Kenneth Marek |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Adult
Male 0301 basic medicine Pathology medicine.medical_specialty Imaging biomarker Pyridines Standardized uptake value amyloid-β Single-photon emission computed tomography single photon emission computed tomography Young Adult 03 medical and health sciences 0302 clinical medicine Alzheimer Disease Animals Humans Medicine Tissue Distribution Aged Aged 80 and over Cerebral Cortex Tomography Emission-Computed Single-Photon Temporal cortex Amyloid beta-Peptides medicine.diagnostic_test business.industry Functional Neuroimaging Imidazoles imaging Original Articles Human brain medicine.disease radiotracer Imaging agent Rats 030104 developmental biology medicine.anatomical_structure Case-Control Studies Biomarker (medicine) Female Neurology (clinical) Alzheimer's disease business Nuclear medicine Alzheimer’s disease Biomarkers 030217 neurology & neurosurgery |
| Zdroj: | Brain |
| ISSN: | 1460-2156 0006-8950 |
| DOI: | 10.1093/brain/awv305 |
| Popis: | Although PET amyloid-β imaging agents are available, they cannot be used with SPECT scanners. Maya et al . report that a novel SPECT imaging agent, 123I-ABC577, has a high affinity for amyloid-β, and differentiates Alzheimer's disease patients from healthy controls, with low non-specific retention in the white matter. Non-invasive imaging of amyloid-β 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-β in the brain. The radio-iodinated imidazopyridine derivative 123 I-ABC577 was designed as a candidate for a novel amyloid-β imaging agent. The binding affinity of 123 I-ABC577 for amyloid-β 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-β 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 ∼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-β in the human brain. The availability of an amyloid-β tracer for single photon emission computed tomography might increase the accessibility of diagnostic imaging for Alzheimer’s disease. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|