48 research outputs found
Imaging Protein Misfolding in the Brain Using β-Sheet Ligands
Neurodegenerative diseases characterized by pathological protein accumulation in cells are termed “proteinopathies.” Although various protein aggregates share cross-β-sheet structures, actual conformations vary among each type of protein deposit. Recent progress in the development of radiotracers for positron emission tomography (PET) has enabled the visualization of protein aggregates in living brains. Amyloid PET tracers have been developed, and are widely used for the diagnosis of Alzheimer’s disease and non-invasive assessment of amyloid burden in clinical trials of anti-dementia drugs. Furthermore, several tau PET tracers have been successfully developed and used in the clinical studies. However, recent studies have identified the presence of off-target binding of radiotracers in areas of tau deposition, suggesting that concomitant neuroinflammatory changes might affect tracer binding. In contrast to amyloid and tau PET, there are no established tracers for imaging Lewy bodies in the human brain. In this review, we describe lessons learned from the development of PET tracers and discuss the future direction of tracer development for protein misfolding diseases
Highlight selection of radiochemistry and radiopharmacy developments by editorial board
Background: The Editorial Board of EJNMMI Radiopharmacy and Chemistry releases a biannual highlight commentary to update the readership on trends in the field of radiopharmaceutical development. Main Body: This commentary of highlights has resulted in 21 different topics selected by each coauthoring Editorial Board member addressing a variety of aspects ranging from novel radiochemistry to first in man application of novel radiopharmaceuticals. Conclusion: Trends in radiochemistry and radiopharmacy are highlighted demonstrating the progress in the research field in various topics including new PET-labelling methods, FAPI-tracers and imaging, and radionuclide therapy being the scope of EJNMMI Radiopharmacy and Chemistry
Dissociation of Tau Deposits and Brain Atrophy in Early Alzheimer’s Disease: A Combined Positron Emission Tomography/Magnetic Resonance Imaging Study
The recent advent of tau-specific positron emission tomography (PET) has enabled in vivo assessment of tau pathology in Alzheimer’s disease (AD). However, because PET scanners have limited spatial resolution, the measured signals of small brain structures or atrophied areas are underestimated by partial volume effects (PVEs). The aim of this study was to determine whether partial volume correction (PVC) improves the precision of measures of tau deposits in early AD. We investigated tau deposits in 18 patients with amyloid-positive early AD and in 36 amyloid-negative healthy controls using 18F-THK5351 PET. For PVC, we applied the SPM toolbox PETPVE12. The PET images were then spatially normalized and subjected to voxel-based group analysis using SPM12 for comparison between the early AD patients and healthy controls. We also compared these two groups in terms of brain atrophy using voxel-based morphometry of MRI. We found widespread neocortical tracer retention predominantly in the posterior cingulate and precuneus areas, but also in the inferior temporal lobes, inferior parietal lobes, frontal lobes, and occipital lobes in the AD patients compared with the controls. The pattern of tracer retention was similar between before and after PVC, suggesting that PVC had little effect on the precision of tau load measures. Gray matter atrophy was detected in the medial/lateral temporal lobes and basal frontal lobes in the AD patients. Interestingly, only a few associations were found between atrophy and tau deposits, even after PVC. In conclusion, PVC did not significantly affect 18F-THK5351 PET measures of tau deposits. This discrepancy between tau deposits and atrophy suggests that tau load precedes atrophy
Preparation and Characterization of Modified Electrode by Self‐Assembling Ferrocene Derivative
Comparison of the binding characteristics of [(18)F]THK-523 and other amyloid imaging tracers to Alzheimer\u27s disease pathology.
PurposeExtensive deposition of senile plaques and neurofibrillary tangles in the brain is a pathological hallmark of Alzheimer disease (AD). Although several PET imaging agents have been developed for in vivo detection of senile plaques, no PET probe is currently available for selective detection of neurofibrillary tangles in the living human brain. Recently, [18F]THK-523 was developed as a potential in vivo imaging probe for tau pathology. The purpose of this study was to compare the binding properties of [18F]THK-523 and other amyloid imaging agents, including PiB, BF-227 and FDDNP, to synthetic protein fibrils and human brain tissue.\nMethodsIn vitro radioligand binding assays were conducted using synthetic amyloid beta42 and K18 deltaK280-tau fibrils. Nonspecific binding was determined by the addition of unlabelled compounds at a concentration of 2 micro M. To examine radioligand binding to neuropathological lesions, in vitro autoradiography was conducted using sections of AD brain.\nResults[18F]THK-523 showed higher affinity for tau fibrils than for Abeta fibrils, whereas the other probes showed a higher affinity for Abeta fibrils. The autoradiographic analysis indicated that [18F]THK-523 accumulated in the regions containing a high density of tau protein deposits. Conversely, PiB and BF-227 accumulated in the regions containing a high density of Abeta plaques.\nConclusionThese findings suggest that the unique binding profile of [18F]THK-523 can be used to identify tau deposits in AD brain
Characteristics of Tau and Its Ligands in PET Imaging
Tau deposition is one of the neuropathological hallmarks in Alzheimer’s disease as well as in other neurodegenerative disorders called tauopathies. Recent efforts to develop selective tau radiopharmaceuticals have allowed the visualization of tau deposits in vivo. In vivo tau imaging allows the assessment of the regional distribution of tau deposits in a single human subject over time for determining the pathophysiology of tau accumulation in aging and neurodegenerative conditions as well as for application in drug discovery of anti-dementia drugs as surrogate markers. However, tau deposits show complicated characteristics because of different isoform composition, histopathology, and ultrastructure in various neurodegenerative conditions. In addition, since tau radiopharmaceuticals possess different chemotype classes, they may show different binding characteristics with heterogeneous tau deposits. In this review, we describe the characteristics of tau deposits and their ligands that have β-sheet binding properties, and the status of tau imaging in clinical studies