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MeerKAT visplots for NGC 6240
No full textAmplitude vs. uv-distance for NGC 6240. The large scale emission of our source peaks at short baselines (indicated by high amplitude points), therefore implying that amplitude is higher at shorter baselines.</p
Gas and stellar kinematics in NGC 6240
No full textWe present results from sub-arcsecond near infrared integral field spectroscopy and millimeter IRAM-interferometry of the interacting galaxy NGC 6240. Using stellar absorption features in the NIR we determined the stellar velocity field and dispersion in NGC 6240. The two NIR emission peaks show rapid rotation and indicate a prograde encounter of the two progenitor galaxies. From the velocity dispersion an excess mass between the two nuclei is detected. This mass can be attributed to a massive rotating disk of cold CO gas located between the nuclei
(18)F-MK-6240 tau-PET in genetic frontotemporal dementia
No full textTau is one of several proteins associated with frontotemporal dementia. While knowing which protein is causing a patient’s disease is crucial, no biomarker currently exists for identifying tau in vivo in frontotemporal dementia. The objective of this study was to investigate the potential for the promising (18)F-MK-6240 PET tracer to bind to tau in vivo in genetic frontotemporal dementia. We enrolled subjects with genetic frontotemporal dementia, who constitute an ideal population for testing because their pathology is already known based on their mutation. Ten participants (three with symptomatic P301L and R406W MAPT mutations expected to show tau binding, three with presymptomatic MAPT mutations and four with non-tau mutations who acted as disease controls) underwent clinical characterization, tau-PET scanning with (18)F-MK-6240, amyloid-PET imaging with (18)F-NAV-4694 to rule out confounding Alzheimer’s pathology, and high-resolution structural MRI. Tau-PET scans of all three symptomatic MAPT carriers demonstrated at least mild (18)F-MK-6240 binding in expected regions, with particularly strong binding in a subject with an R406W MAPT mutation (known to be associated with Alzheimer’s like neurofibrillary tangles). Two asymptomatic MAPT carriers estimated to be 5 years from disease onset both showed modest (18)F-MK-6240 binding, while one ∼30 years from disease onset did not exhibit any binding. Additionally, four individuals with symptomatic frontotemporal dementia caused by a non-tau mutation were scanned (two C9orf72; one GRN; one VCP): (18)F-MK-6240 scans were negative for three subjects, while one advanced C9orf72 case showed minimal regionally non-specific binding. All 10 amyloid-PET scans were negative. Furthermore, a general linear model contrasting genetic frontotemporal dementia subjects to a set of 83 age-matched controls showed significant binding only in the MAPT carriers in selected frontal, temporal and subcortical regions. In summary, our findings demonstrate mild but significant binding of MK-6240 in amyloid-negative P301L and R406W MAPT mutation subjects, with higher standardized uptake value ratio in the R406W mutation associated with the presence of NFTs, and little non-specific binding. These results highlight that a positive (18)F-MK-6240 tau-PET does not necessarily imply a diagnosis of Alzheimer’s disease and point towards a potential use for (18)F-MK-6240 as a biomarker in certain tauopathies beyond Alzheimer’s, although further patient recruitment and autopsy studies will be necessary to determine clinical applicability
18F-MK-6240 tau PET in patients at-risk for chronic traumatic encephalopathy
No full textBackgroundMolecular biomarkers of chronic traumatic encephalopathy (CTE) are lacking. We evaluated 18F-MK-6240 tau PET as a biomarker for CTE. Two studies were done: (1) 3H-MK-6240 autoradiography and an in-vitro brain homogenate binding studies on postmortem CTE tissue, (2) an in-vivo18F-MK-6240 tau PET study in former American football players.MethodsAutoradiography and in-vitro binding studies were done using 3H-MK-6240 on frozen temporal and frontal cortex tissue from six autopsy cases with stage III CTE compared to Alzheimer’s disease. Thirty male former National Football League (NFL) players with cognitive concerns (mean age = 58.9, SD = 7.8) completed tau (18F-MK-6240) and Aβ (18F-Florbetapir) PET. Controls included 39 Aβ-PET negative, cognitively normal males (mean age = 65.7, SD = 6.3). 18F-MK-6240 SUVr images were created using 70–90 min post-injection data with inferior cerebellar gray matter as the reference. We compared SUVr between players and controls using voxelwise and region-of-interest approaches. Correlations between 18F-MK-6240 SUVr and cognitive scores were tested.ResultsAll six CTE stage III cases had Braak NFT stage III but no neuritic plaques. Two had Thal Phase 1 for Aβ; one showed a laminar pattern of 3H-MK-6240 autoradiography binding in the superior temporal cortex and less so in the dorsolateral frontal cortex, corresponding to tau-immunoreactive lesions detected using the AT8 antibody (pSer202/pThr205 tau) in adjacent tissue sections. The other CTE cases had low frequencies of cortical tau-immunoreactive deposits and no well-defined autoradiography binding. In-vitro 3H-MK-6240 binding studies to CTE brain homogenates in the case with autoradiography signal indicated high binding affinity (KD = 2.0 ± 0.9 nM, Bmax = 97 ± 24 nM, n = 3). All NFL players had negative Aβ-PET. There was variable, low-to-intermediate intensity 18F-MK-6240 uptake across participants: 16 had no cortical signal, 7 had medial temporal lobe (MTL) uptake, 2 had frontal uptake, and 4 had MTL and frontal uptake. NFL players had higher SUVr in the entorhinal cortex (d = 0.86, p = 0.001), and the parahippocampal gyrus (d = 0.39, p = 0.08). Voxelwise regressions showed increased uptake in NFL players in two bilateral anterior MTL clusters (p < 0.05 FWE). Higher parahippocampal and frontal–temporal SUVrs correlated with worse memory (r = -0.38, r = -0.40) and semantic fluency (r = -0.38, r = -0.48), respectively.ConclusionWe present evidence of 3H-MK-6240 in-vitro binding to post-mortem CTE tissue homogenates and in vivo 18F-MK-6240 PET binding in the MTL among a subset of participants. Additional studies in larger samples and PET-to-autopsy correlations are required to further elucidate the potential of 18F-MK-6240 to detect tau pathology in CTE
In vivo quantification of neurofibrillary tangles with [18F]MK-6240
No full textAbstract Background Imaging agents capable of quantifying the brain’s tau aggregates will allow a more precise staging of Alzheimer’s disease (AD). The aim of the present study was to examine the in vitro properties as well as the in vivo kinetics, using gold standard methods, of the novel positron emission tomography (PET) tau imaging agent [18F]MK-6240. Methods In vitro properties of [18F]MK-6240 were estimated with autoradiography in postmortem brain tissues of 14 subjects (seven AD patients and seven age-matched controls). In vivo quantification of [18F]MK-6240 binding was performed in 16 subjects (four AD patients, three mild cognitive impairment patients, six healthy elderly individuals, and three healthy young individuals) who underwent 180-min dynamic scans; six subjects had arterial sampling for metabolite correction. Simplified approaches for [18F]MK-6240 quantification were validated using full kinetic modeling with metabolite-corrected arterial input function. All participants also underwent amyloid-PET and structural magnetic resonance imaging. Results In vitro [18F]MK-6240 uptake was higher in AD patients than in age-matched controls in brain regions expected to contain tangles such as the hippocampus, whereas no difference was found in the cerebellar gray matter. In vivo, [18F]MK-6240 displayed favorable kinetics with rapid brain delivery and washout. The cerebellar gray matter had low binding across individuals, showing potential for use as a reference region. A reversible two-tissue compartment model well described the time–activity curves across individuals and brain regions. Distribution volume ratios using the plasma input and standardized uptake value ratios (SUVRs) calculated after the binding approached equilibrium (90 min) were correlated and higher in mild cognitive impairment or AD dementia patients than in controls. Reliability analysis revealed robust SUVRs calculated from 90 to 110 min, while earlier time points provided inaccurate estimates. Conclusions This evaluation shows an [18F]MK-6240 distribution in concordance with postmortem studies and that simplified quantitative approaches such as the SUVR offer valid estimates of neurofibrillary tangle load 90 min post injection. [18F]MK-6240 is a promising tau tracer with the potential to be applied in the disease diagnosis and assessment of therapeutic interventions
[18F]MK-6240 Radioligand Delivery Indices as Surrogates of Cerebral Perfusion: Bias and Correlation Against [15O]Water.
Get PDF[ 18F]MK-6240 PET (where MK-6240 is 6-(fluoro)-3-(1H-pyrrolo[2,3-c]pyridin-1-yl)isoquinolin-5-amine) is used to assess in vivo tau deposition across the Alzheimer disease (AD) spectrum. We aimed to quantify the associations and bias of early-frame [ 18F]MK-6240 PET as surrogates for cerebral perfusion against gold standard [ 15O]water PET and the potential impact of cerebral perfusion on [ 18F]MK-6240 tau quantification across aging and the AD spectrum. Methods: Fourteen cognitively normal (CN, 4 young CN and 10 old CN) and 3 AD participants underwent dynamic [ 18F]MK-6240 PET, with 9 undergoing arterial sampling. A subset ( n = 11) underwent [ 15O]water PET. [ 18F]MK-6240 perfusion indices were estimated as radiotracer delivery indices K 1 (using 2-tissue-compartment models), and relative perfusion indices were estimated as R 1 (using compartmental and reference tissue models, cerebellar gray matter reference region) and early-frame SUV ratio (0-3 min). [ 15O]water K 1 and R 1 were estimated using 1-tissue-compartment models). [ 18F]MK-6240 tau burden was estimated using distribution volume ratio and SUV ratio at 90-110 min. Spearman correlations, linear mixed-effect models, and Bland-Altman analyses examined relationships between [ 18F]MK-6240 perfusion indices against [ 15O]water and between estimates of perfusion and tau burden in tau-relevant regions. The impact of partial-volume correction was examined. Results: Significant correlations were observed between [ 18F]MK-6240 K 1 and [ 15O]water K 1 (ρ = 0.57); However, [ 18F]MK-6240 K 1 underestimated [ 15O]water K 1 by up to 50%, with a strong negative proportional bias. Significant correlations were observed between [ 18F]MK-6240 relative perfusion and [ 15O]water R 1 (ρ > 0.84), with minimal bias. In 2 AD participants, significant correlations were observed between perfusion and [ 18F]MK-6240 retention. Applying partial-volume correction did not significantly impact the correlations or improve the underestimations in [ 18F]MK-6240 K 1 Conclusion: Using head-to-head [ 18F]MK-6240 and [ 15O]water data, we showed that [ 18F]MK-6240 exhibited a relatively low extraction fraction, leading to underestimation of cerebral perfusion. Our results provide further support for [ 18F]MK-6240 R 1 as a reliable estimate of relative cerebral perfusion, with strong associations and minimal bias compared with [ 15O]water. In addition, lower perfusion may be associated with higher [ 18F]MK-6240 retention in tau-relevant regions in AD. These findings further support the use of dynamic [ 18F]MK-6240 in dual-imaging assessments of tau burden and vascular health. </p
Gas Dynamics in the Luminous Merger NGC 6240
No full textWe report 0.5"x0.9" resolution, interferometric observations of the 1.3 mm CO J=2-1 line in the infrared luminous galactic merger NGC 6240. About half of the CO flux is concentrated in a rotating but highly turbulent, thick disk structure centered between the two radio and near-infrared nuclei. A number of gas features connect this ~500 pc diameter central disk to larger scales. Throughout this region the molecular gas has local velocity widths which exceed 300 km/s FWHM and even reach FWZP line widths of 1000 km/s in a number of directions. The mass of the central gas concentration constitutes a significant fraction of the dynamical mass, M_gas(R<470 pc) ~ 2-4x10^9 M_o ~ 0.3-0.7 M_dyn. We conclude that NGC 6240 is in an earlier merging stage than the prototypical ultraluminous galaxy, Arp 220. The interstellar gas in NGC 6240 is in the process of settling between the two progenitor stellar nuclei, is dissipating rapidly and will likely form a central thin disk. In the next merger stage, NGC 6240 may well experience a major starburst like that observed in Arp 220
Gas dynamics in the luminous merger NGC 6240
No full textWe report 0.5 x 0.9 resolution, interferometric observations of the 1.3 mm CO J=2#->#1 line in the infrared luminous galactic merger NGC 6240. About half of the CO flux is concentrated in a rotating but highly turbulent, thick disk structure centered between the two radio and near-infrared nuclei. A number of gas features connect this #approx#500 pc diameter central disk to larger scales. Throughout this region the molecular gas has local velocity widths which exceed 300 km s"-"1 FWHM and even reach FWZP line widths of 1000 km s"-"1 in a number of directions. The mass of the central gas concentration constitutes a significant fraction of the dynamical mass, M_g_a_s(R#<=#470 pc)#propor to#2-4 x 10"9 M_sun#propor to#0.3-0.7 M_d_y_n. We conclude that NGC 6240 is in an earlier merging stage than the prototypical ultraluminous galaxy, Arp 220. The interstellar gas in NGC 6240 is in the process of settling between the two progenitor stellar nuclei, is dissipating rapidly and will likely form a central thin disk. In the next merger stage, NGC 6240 may well experience a major starburst like that observed in Arp 220. (orig.)SIGLEAvailable from TIB Hannover: RN 9303(465) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman
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