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| 2. |
- Osborn, H. P., et al.
(författare)
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The PDS 110 observing campaign - photometric and spectroscopic observations reveal eclipses are aperiodic
- 2019
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 485:2, s. 1614-1625
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Tidskriftsartikel (refereegranskat)abstract
- PDS 110 is a young disc-hosting star in the Orion OB1A association. Two dimming events of similar depth and duration were seen in 2008 (WASP) and 2011 (KELT), consistent with an object in a closed periodic orbit. In this paper, we present data from a ground-based observing campaign designed to measure the star both photometrically and spectroscopically during the time of predicted eclipse in 2017 September. Despite high-quality photometry, the predicted eclipse did not occur, although coherent structure is present suggesting variable amounts of stellar flux or dust obscuration. We also searched for radial velocity (RV) oscillations caused by any hypothetical companion and can rule out close binaries to 0.1Ms. Asearch of Sonneberg plate archive data also enabled us to extend the photometric baseline of this star back more than 50 yr, and similarly does not re-detect any deep eclipses. Taken together, they suggest that the eclipses seen in WASP and KELT photometry were due to aperiodic events. It would seem that PDS 110 undergoes stochastic dimmings that are shallower and of shorter duration than those of UX Ori variables, but may have a similar mechanism.
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| 3. |
- Tissot, C., et al.
(författare)
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The Association of Age-Related and Off-Target Retention with Longitudinal Quantification of 18F MK6240 Tau PET in Target Regions
- 2023
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Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 2159-662X. ; 64:3, s. 452-459
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Tidskriftsartikel (refereegranskat)abstract
- 6-(fluoro-18F)-3-(1H-pyrrolo[2,3-c]pyridin-1-yl)isoquinolin-5-amine ([18F] MK6240) tau PET tracer quantifies the brain tau neurofibrillary tangle load in Alzheimer disease. The aims of our study were to test the stabil-ity of common reference region estimates in the cerebellum over time and across diagnoses and evaluate the effects of age-related and off -target retention on the longitudinal quantification of [18F]MK6240 in tar-get regions. Methods: We assessed reference, target, age-related, and off-target regions in 125 individuals across the aging and Alzhei-mer disease spectrum with longitudinal [18F]MK6240 SUVs and SUV ratios (SUVRs) (mean +/- SD, 2.25 +/- 0.40 y of follow-up). We obtained SUVR from meninges, exhibiting frequent off-target retention with [18F]MK6240. Additionally, we compared tracer uptake between 37 cognitively unimpaired young (CUY) (mean age, 23.41 +/- 3.33 y) and 27 cognitively unimpaired older (CU) adults (amyloid-P-negative and tau-negative, 58.50 +/- 9.01 y) to identify possible nonvisually apparent, age-related signal. Two-tailed t testing and Pearson correlation testing were used to determine the difference between groups and associa-tions between changes in region uptake, respectively. Results: Inferior cerebellar gray matter SUV did not differ on the basis of diagnosis and amyloid-P status, cross-sectionally and over time. [18F]MK6240 uptake significantly differed between CUY and CU adults in the puta-men or pallidum (affecting-75% of the region) and in the Braak II region (affecting-35%). Changes in meningeal and putamen or palli-dum SUVRs did not significantly differ from zero, nor did they vary across diagnostic groups. We did not observe significant correlations between longitudinal changes in age-related or meningeal off-target retention and changes in target regions, whereas changes in all target regions were strongly correlated. Conclusion: Inferior cerebellar gray matter was similar across diagnostic groups cross-sectionally and sta-ble over time and thus was deemed a suitable reference region for quantification. Despite not being visually perceptible, [18F]MK6240 has age-related retention in subcortical regions, at a much lower magnitude but topographically colocalized with significant off-target signal of the first-generation tau tracers. The lack of correlation between changes in age-related or meningeal and target retention suggests little influence of possible off-target signals on longitudinal tracer quantification. Nev-ertheless, the age-related retention in the Braak II region needs to be further investigated. Future postmortem studies should elucidate the source of the newly reported age-related [18F]MK6240 signal, and in vivo studies should further explore its impact on tracer quantification.
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| 4. |
- Lindberg, Anton, et al.
(författare)
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Radiosynthesis, In Vitro and In Vivo Evaluation of [F-18]CBD-2115 as a First-in-Class Radiotracer for Imaging 4R-Tauopathies
- 2021
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Ingår i: ACS Chemical Neuroscience. - : AMER CHEMICAL SOC. - 1948-7193. ; 12:4, s. 596-602
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Tidskriftsartikel (refereegranskat)abstract
- CBD-2115 was selected from a library of 148 compounds based on a pyridinyl-indole scaffold as a first-in-class 4R-tau radiotracer. In vitro binding assays showed [H-3]CBD-2115 had a K-D value of 6.9 nM and a nominal B-max of 500 nM in 4R-tau expressing P301L transgenic mouse tissue. In binding assays with human brain tissue homogenates, [H-3]CBD-2115 has a higher affinity (4.9 nM) for progressive supranuclear palsy specific 4R-tau deposits than [H-3]flortaucipir (45 nM) or [H-3]MK-6240 (>50 nM). [F-18]CBD-2115 was reliably synthesized (3-11% radiochemical yield with molar activity of 27-111 GBq/mu mol and >97% radiochemical purity). Dynamic PET imaging was conducted in mice, rats, and nonhuman primates, and all species showed initial brain uptake of 0.5-0.65 standardized uptake value with fast clearance from normal tissues. [H-3]CBD-2115 could be a useful lead radioligand for further research in 4R-tauopathies, and PET radiotracer development will focus on improving brain uptake and binding affinity.
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- Villemagne, Victor L., et al.
(författare)
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CenTauR : Toward a universal scale and masks for standardizing tau imaging studies
- 2023
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Ingår i: Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring. - 2352-8729. ; 15:3
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Recently, an increasing number of tau tracers have become available. There is a need to standardize quantitative tau measures across tracers, supporting a universal scale. We developed several cortical tau masks and applied them to generate a tau imaging universal scale. METHOD: One thousand forty-five participants underwent tau scans with either 18F-flortaucipir, 18F-MK6240, 18F-PI2620, 18F-PM-PBB3, 18F-GTP1, or 18F-RO948. The universal mask was generated from cognitively unimpaired amyloid beta (Aβ)− subjects and Alzheimer's disease (AD) patients with Aβ+. Four additional regional cortical masks were defined within the constraints of the universal mask. A universal scale, the CenTauRz, was constructed. RESULTS: None of the regions known to display off-target signal were included in the masks. The CenTauRz allows robust discrimination between low and high levels of tau deposits. DISCUSSION: We constructed several tau-specific cortical masks for the AD continuum and a universal standard scale designed to capture the location and degree of abnormality that can be applied across tracers and across centers. The masks are freely available at https://www.gaain.org/centaur-project.
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