Β-amyloid Positron Emission Tomography Imaging Research Articles

Novel β-amyloid PET Imaging Study of [18F]92 in Patients with Cognitive Decline.

[18F]-4-((E)-(((E)-4-(2-(2-(2-Fluoroethoxy)ethoxy)ethoxy)benzylidene)-hydrazono)methyl)-N-methylaniline ([18F]92) is a novel positron emission tomography (PET) tracer previously reported to exhibit high binding affinity to aggregated β-amyloid (Aβ). This study aims to report a fully automated radiosynthesis procedure for [18F]92, explore its radioactive distribution in the brains of healthy subjects, and investigate its potential application value in the early diagnosis of Alzheimer's disease (AD). The fully automated radiosynthesis of [18F]92 was performed on the AllinOne module. Thirty one participants were recruited for this study. Dynamic [18F]92 PET imaging was conducted over 0-90 min period to assess time-activity curves (TAC) and standardized uptake value ratio (SUVR) curves in cognitively normal (CN) subjects. All participants were visually classified as either positive (+) or negative (-). Semiquantitative analyses of [18F]92 were performed by calculating SUVRs in different regions of interest. Furthermore, the study analyzed the relationships between global SUVR and plasma AD biomarkers, including Aβ42, Aβ40, P-tau181, and T-tau. The automated radiosynthesis of [18F]92 was completed within 50 min, yielding a radiochemical purity of greater than 95% and a radiochemical yield of 36 ± 3% (nondecay-corrected). Among the participants, 15 were estimated as Aβ (-) and 16 as Aβ (+). TACs indicated that [18F]92 rapidly crossed the blood-brain barrier within 10 min, followed by a rapid decrease, which then slowed down in the last 50-90 min. SUVR curves revealed that SUVR values stabilized around 60-70 min after injection and reached an equilibrium between 70 and 90 min, primarily in the cerebral cortex. SUVRs of Aβ (+) participants were significantly higher than those of Aβ (-) individuals within the cerebral cortex. In addition, Aβ42 and the Aβ42/Aβ40 ratio exhibited negative correlations with global SUVR, while plasma P-tau181 and the P-tau181/T-tau ratio displayed positive correlations with global SUVR. [18F]92 exhibits excellent pharmacokinetic properties in the human brain and can be synthesized automatically on a large scale. [18F]92 is a promising and reliable radiotracer for estimating Aβ pathology accumulation, providing valuable assistance in AD diagnosis and guiding clinical trials of therapeutic drugs.

Clinical Utility of β-Amyloid PET Imaging in People Living With HIV With Cognitive Symptoms.

Imaging with β-amyloid (Aβ) positron emission tomography (PET) has the potential to aid the diagnosis of the cause of cognitive impairment affecting people living with HIV (PLWH) when neurodegenerative disorders are considered. We evaluated the clinical utility of [18F]Florbetaben (FBB) in PLWH with cognitive symptoms. Imaging with FBB PET was performed in 20 patients with cognitive concerns about dementia. Neuropsychological testing, plasma neurofilament light protein, plasma Aβ40, Aβ42, and cerebrospinal fluid Aβ42, tau, and HIV RNA were obtained. FBB PET images were assessed visually by 3 readers blinded to the clinical diagnosis and quantitatively by obtaining a composite cortical to cerebellar cortex standardized uptake value ratio (SUVR). FBB SUVR from 10 age-matched healthy controls was compared with SUVR of PLWH. Most participants were men (90%) of white ethnicity (90%) with a median age (interquartile range) of 59 (43-79) years. Median CD4 count was 682 (74-1056). All patients were on combination antiretroviral therapy with plasma and cerebrospinal fluid HIV RNA <40 copies/mL. Fourteen patients had objective cognitive impairment including 2 who met clinical criteria for a diagnosis of dementia. No significant differences in composite SUVRs between PLWH and controls [mean (SD): 1.18 (0.03) vs. 1.16 (0.09); P = 0.37] were observed. Four patients were FBB+ with the highest SUVR in the posterior cingulate, superior temporal, and frontal superior lobe. Amyloid PET results contributed to a change in diagnosis and treatment for 10 patients. [18F]Florbetaben PET has potential as an adjunctive tool in the diagnosis of PLWH with cognitive impairment, increasing diagnostic certainty and optimizing management.

Therapeutic effect of mesenchymal stem cells in an animal model of Alzheimer's disease evaluated by β-amyloid positron emission tomography imaging.

We evaluated the effects of bone marrow-derived mesenchymal stem cells in a model of Alzheimer's disease using serial [18F]Florbetaben positron emission tomography. 3xTg Alzheimer's disease mice were treated with intravenously injected bone marrow-derived mesenchymal stem cells, and animals without stem cell therapy were used as controls. Serial [18F]Florbetaben positron emission tomography was performed after therapy. The standardized uptake value ratio was measured as the cortex standardized uptake value divided by the cerebellum standardized uptake value. Memory function and histological changes were observed using the Barnes maze test and β-amyloid-reactive cells. Standardized uptake value ratio decreased significantly from day 14 after stem cell administration in the bone marrow-derived mesenchymal stem cells-treated group (n = 28). In contrast, there was no change in the ratio in control mice (n = 25) at any time point. In addition, mice that received bone marrow-derived mesenchymal stem cell therapy also exhibited significantly better memory function and less β-amyloid-immunopositive plaques compared to controls. The therapeutic effect of intravenously injected bone marrow-derived mesenchymal stem cells in a mouse model of Alzheimer's disease was confirmed by β-amyloid positron emission tomography imaging, memory functional studies and histopathological evaluation.

AV-1451 PET imaging of tau pathology in preclinical Alzheimer disease: Defining a summary measure

Utilizing [18F]-AV-1451 tau positron emission tomography (PET) as an Alzheimer disease (AD) biomarker will require identification of brain regions that are most important in detecting elevated tau pathology in preclinical AD. Here, we utilized an unsupervised learning, data-driven approach to identify brain regions whose tau PET is most informative in discriminating low and high levels of [18F]-AV-1451 binding. 84 cognitively normal participants who had undergone AV-1451 PET imaging were used in a sparse k-means clustering with resampling analysis to identify the regions most informative in dividing a cognitively normal population into high tau and low tau groups. The highest-weighted FreeSurfer regions of interest (ROIs) separating these groups were the entorhinal cortex, amygdala, lateral occipital cortex, and inferior temporal cortex, and an average SUVR in these four ROIs was used as a summary metric for AV-1451 uptake. We propose an AV-1451 SUVR cut-off of 1.25 to define high tau as described by imaging. This spatial distribution of tau PET is a more widespread pattern than that predicted by pathological staging schemes. Our data-derived metric was validated first in this cognitively normal cohort by correlating with early measures of cognitive dysfunction, and with disease progression as measured by β-amyloid PET imaging. We additionally validated this summary metric in a cohort of 13 Alzheimer disease patients, and showed that this measure correlates with cognitive dysfunction and β-amyloid PET imaging in a diseased population.