A5065225018- Alzheimer's disease research and treatments
- Dementia and Cognitive Impairment Research
- Medical Imaging Techniques and Applications
- Neuroscience and Neuropharmacology Research
- Cholinesterase and Neurodegenerative Diseases
- Functional Brain Connectivity Studies
- Parkinson's Disease Mechanisms and Treatments
- Computational Drug Discovery Methods
- Advanced MRI Techniques and Applications
- Lanthanide and Transition Metal Complexes
- Advanced Neuroimaging Techniques and Applications
- Olfactory and Sensory Function Studies
- Neurological Disease Mechanisms and Treatments
- Mast cells and histamine
- S100 Proteins and Annexins
- Phytochemistry and biological activity of medicinal plants
- Pharmacological Effects of Natural Compounds
- Neuroinflammation and Neurodegeneration Mechanisms
- Sleep and Wakefulness Research
- Radiopharmaceutical Chemistry and Applications
- Amino Acid Enzymes and Metabolism
- Ginseng Biological Effects and Applications
- Receptor Mechanisms and Signaling
- Diet and metabolism studies
- Allergic Rhinitis and Sensitization
Tohoku Medical and Pharmaceutical University
2016-2024
Tohoku University
2015-2024
Japan Radioisotope Association
1996-2024
San Francisco VA Medical Center
2024
University of California, San Francisco
2024
Tohoku Medical and Pharmaceutical University Hospital
2018-2023
Tohoku University Hospital
2022-2023
American Pharmacists Association
2022
Fukuyama University
2003-2020
Nagoya City University
2020
seminal plasma (Okamura, N., and Sugita, Y. (1983
While considerable effort has focused on developing positron emission tomography β-amyloid imaging radiotracers for the early diagnosis of Alzheimer's disease, no radiotracer is available non-invasive quantification tau. In this study, we detail characterization 18F-THK523 as a novel tau radiotracer. vitro binding studies demonstrated that binds with higher affinity to greater number sites recombinant (K18Δ280K) compared β-amyloid1–42 fibrils. Autoradiographic and histofluorescence analysis...
Imaging of neurofibrillary pathology in the brain helps diagnosing dementia, tracking disease progression, and evaluating therapeutic efficacy antidementia drugs. The radiotracers used this imaging must be highly sensitive specific for tau protein fibrils human brain. We developed a novel PET tracer, <sup>18</sup>F-THK5351, through compound optimization arylquinoline derivatives. <b>Methods:</b> vitro binding properties, pharmacokinetics, safety <sup>18</sup>F-THK5351 were investigated,...
18F-THK5351 is a quinoline-derived tau imaging agent with high affinity to paired helical filaments (PHF). However, levels of retention in brain regions thought contain negligible concentrations PHF raise questions about the interpretation positron emission tomography (PET) signals, particularly given previously described interactions between quinolone derivatives and monoamine oxidase B (MAO-B). Here, we tested effects MAO-B inhibition on uptake using PET autoradiography. Eight participants...
Neurofibrillary tangles in Alzheimer disease (AD) brains are composed of the microtubule-associated protein tau. Noninvasive monitoring tau aggregates living brain will provide useful information regarding pathophysiology AD. However, no PET probes currently available for selective detection pathology We have previously reported <sup>18</sup>F-labeled THK-523 (<sup>18</sup>F-6-(2-fluoroethoxy)-2-(4-aminophenyl)quinoline) as a imaging radiotracer candidate PET. After compound optimization, we...
Non-invasive imaging of tau pathology in the living brain would be useful for accurately diagnosing Alzheimer's disease, tracking disease progression, and evaluating treatment efficacy disease-specific therapeutics. In this study, we evaluated clinical usefulness a novel tau-imaging positron emission tomography tracer 18F-THK5105 16 human subjects including eight patients with (three male five females, 66–82 years) healthy elderly controls 63–76 years). All participants underwent...
Evidence supporting the hypothesis that reduced cerebrospinal fluid (CSF) clearance is involved in pathophysiology of Alzheimer disease (AD) comes primarily from rodent models. However, unlike rodents, which predominant extracranial CSF egress via olfactory nerves traversing cribriform plate, human pathways are not well characterized. Dynamic PET with <sup>18</sup>F‐THK5117, a tracer for tau pathology, was used to estimate ventricular time–activity as biomarker clearance. We tested 3...
Extensive deposition of dense amyloid fibrils is a characteristic neuropathologic hallmark in Alzheimer9s disease (AD). Noninvasive detection these molecules potentially useful for early and precise patients with AD. This study reports novel compound, 2-(2-[2-dimethylaminothiazol-5-yl]ethenyl)-6-(2-[fluoro]ethoxy)benzoxazole (BF-227), vivo deposits using PET. <b>Methods:</b> The binding affinity BF-227 to amyloid-β (Aβ) was calculated. property plaques evaluated by staining AD brain...
Neurofibrillary tangles (NFTs), neuropil threads, and neuritic elements of senile plaques predominantly comprise hyperphosphorylated tau protein represent pathological characteristics Alzheimer's disease (AD). These lesions occur before the presentation clinical symptoms correlate with severity dementia. In vivo detection these would thus prove useful for preclinical diagnosis AD tracking progression. The present study introduces three novel compounds, 4-[2-(2-benzoimidazolyl)ethenyl]- N ,...
Antioxidant components in Aloe vera were examined for lipid peroxidation using rat liver microsomal and mitochondrial enzymes. Among the aloesin derivatives examined, isorabaichromone showed a potent antioxidative activity. The DPPH radical superoxide anion scavenging activities determined. As one of most components, together with feruloylaloesin p-coumaroylaloesin activities. Electron spin resonance (ESR) trapping method suggested that activity may have been due to its caffeoyl group. A....
When 32P-labeled human neutrophils were activated by exposure to phorbol myristate acetate, three 48-kDa proteins (designated pp48/6.8, pp48/7.3, and pp48/7.8, from their isoelectric points) found have become labeled. With maximal stimulation, labeling was complete 30 s. lesser degrees of the extent at 2 min correlated with rates production phorbol-treated cells. Increased these also seen in cells exposed f-Met-Leu-Phe. In patients X-linked cytochrome b558-negative chronic granulomatous...
Clinical PET studies using <sup>18</sup>F-THK5351 have demonstrated significant tracer retention in sites susceptible to tau burden Alzheimer disease (AD). However, the vivo signal reflect aggregates remains controversial. <b>Methods:</b> We examined spatial pattern of binding, amyloid-β, tau, and gliosis an autopsy-confirmed AD patient who underwent <sup>11</sup>C-Pittsburgh compound B before death. <b>Results:</b> Regional was significantly correlated with density neocortex monoamine...
PET provides a noninvasive means to evaluate the functional integrity of presynaptic monoaminergic system in living human brain. <b>Methods:</b> In this study, novel <sup>18</sup>F-labeled tetrabenazine derivative, <sup>18</sup>F-(+)fluoropropyldihydrotetrabenazine (<sup>18</sup>F-AV-133), was used for assessment vesicular monoamine transporters type 2 (VMAT2) 17 Parkinson disease (PD) patients and 6 healthy controls. The binding potential (BP) <sup>18</sup>F-AV-133 calculated using Logan...
To determine whether 18F-THK5351 PET can be used to visualize tau deposits in brain lesions live patients with corticobasal syndrome (CBS).We evaluated the vitro binding of 3H-THK5351 postmortem tissues from a patient degeneration (CBD). In clinical studies, retention 5 CBS was compared that 8 age-matched normal controls and Alzheimer disease (AD).3H-THK5351 able bind CBD. showed significantly higher frontal, parietal, globus pallidus than AD. Higher observed contralaterally side associated...
The aim of this study was to compare the binding properties several tau positron emission tomography tracers-THK5117, THK5351, T807 (also known as AV1451; flortaucipir), and PBB3-head head in same human brain tissue.Binding assays were performed regional distribution 3H-THK5117 3H-THK5351 postmortem tissue from three Alzheimer's disease (AD) cases control subjects frontal temporal cortices well hippocampus. Competition between THK5117, PBB3, T807, off-target THK5117 toward monoamine oxidase...
Background: Imaging studies in Alzheimer's disease (AD) have yet to answer the underlying questions concerning relationship among tau retention, neuroinflammation, network disruption and cognitive decline. We compared spatial retention patterns of 18F-THK5351 resting state (RSN) patients with early AD healthy controls. Methods: enrolled 23 11C-Pittsburgh compound B (PiB)-positive 24 11C-PiB-negative participants as All underwent functional MRI PET scans. used scaled subprofile...
Background [18F]THK5351, a recently-developed positron emission tomography (PET) tracer for measuring tau neurofibrillary tangle accumulation, may help researchers examine aging, disease, and pathology in living human brains. We examined THK5351 pharmacokinetics to define an optimal acquisition time static late images. Methods Primary measurements were calculation of regional values distribution volume ratios (DVR) standardized uptake value (SUVR) 6 healthy older control 10 Alzheimer's...