IC-P-171: MENTAL AND PHYSICAL ACTIVITY DURING THE 80-MINUTE UPTAKE TIME AFFECTS OFF-TARGET BINDING IN TAU PET SCANS (18F-FTP)

Purpose: Semi-quantitative PET measures can be affected by changes in blood flow, whereas quantitative measures are not. The aim of the study was to compare semi-quantitative(SUVr) and quantitative(R1, BPND) parameters of longitudinal tau PET scans with [18F]flortaucipir, with respect to changes in blood flow. Methods: Subjects with subjective cognitive decline(SCD; n=38) and Alzheimer′s disease(AD) patients(n=24) underwent baseline(BL) and 2-year follow-up(FU) dynamic [18F]flortaucipir PET scans. BPND and R1 were estimated using RPM and SUVr(80-100min) was calculated (cerebellar gray as reference). For each region-of-interest ((trans)entorhinal, limbic and neocortical) and parameter, %change was calculated. Regional SUVrs were compared to corresponding DVR (= BPND+1) using paired T-tests. Additionally, simulations were performed to model effects of flow changes on BPND and SUVr in different binding categories. Thereafter, %bias for SUVr with respect to underlying binding and flow were evaluated. Results: In SCD, there was a difference between %change in the (trans)entorhinal ROI (DVR 2.56% vs SUVr 1.85%) only. In AD, a difference was found in the limbic ROI (DVR 6.61% vs SUVr 7.52%) only. R1 changes were small(+0.7% in SCD and -1.6% in AD). Simulations illustrated with increasing flow a decreased %bias for SUVr in low binding conditions, whereas a slightly increased bias was observed in high binding conditions. Conclusion: SUVr provided an accurate estimate of specific binding for [18F]flortaucipir over a two-year follow-up. However, simulations showed that flow changes can affect [18F]flortaucipir SUVr, hence DVR/BPND should be preferred in more advanced disease stages and/or conditions that could induce significant flow changes like pharmacotherapeutic interventions.

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IC-P-184: Comparison of Early Dynamic Amyloid and TAU-PET Scans to 18 F-FDG-PET image

Alzheimer s & Dementia ◽

10.1016/j.jalz.2016.06.215 ◽

2016 ◽

Vol 12 ◽

pp. P134-P134

Author(s):

Gareth R. Jones ◽

Victor L. Villemagne ◽

Tia L. Cummins ◽

Christopher C. Rowe

Keyword(s):

Fdg Pet ◽

Tau Pet ◽

Pet Scans

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Clinical validity of increased cortical binding of tau ligands of the THK family and PBB3 on PET as biomarkers for Alzheimer’s disease in the context of a structured 5-phase development framework

European Journal of Nuclear Medicine and Molecular Imaging ◽

10.1007/s00259-021-05277-4 ◽

2021 ◽

Author(s):

Konstantinos Chiotis ◽

Alessandra Dodich ◽

Marina Boccardi ◽

Cristina Festari ◽

Alexander Drzezga ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Diagnostic Accuracy ◽

Preliminary Evidence ◽

Imaging Biomarkers ◽

Clinical Validity ◽

Development Framework ◽

Phase Development ◽

Tau Pet ◽

Target Binding

Abstract Purpose The research community has focused on defining reliable biomarkers for the early detection of the pathological hallmarks of Alzheimer’s disease (AD). In 2017, the Geneva AD Biomarker Roadmap initiative adapted the framework for the systematic validation of oncological biomarkers to AD, with the aim to accelerate their development and implementation in clinical practice. The aim of this work was to assess the validation status of tau PET ligands of the THK family and PBB3 as imaging biomarkers for AD, based on the Biomarker Roadmap methodology. Methods A panel of experts in AD biomarkers convened in November 2019 at a 2-day workshop in Geneva. The level of clinical validity of tau PET ligands of the THK family and PBB3 was assessed based on the 5-phase development framework before the meeting and discussed during the workshop. Results PET radioligands of the THK family discriminate well between healthy controls and patients with AD dementia (phase 2; partly achieved) and recent evidence suggests an accurate diagnostic accuracy at the mild cognitive impairment (MCI) stage of the disease (phase 3; partly achieved). The phases 2 and 3 were considered not achieved for PBB3 since no evidence exists about the ligand’s diagnostic accuracy. Preliminary evidence exists about the secondary aims of each phase for all ligands. Conclusion Much work remains for completing the aims of phases 2 and 3 and replicating the available evidence. However, it is unlikely that the validation process for these tracers will be completed, given the presence of off-target binding and the development of second-generation tracers with improved binding and pharmacokinetic properties.

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Tauvid™: The First FDA-Approved PET Tracer for Imaging Tau Pathology in Alzheimer’s Disease

Pharmaceuticals ◽

10.3390/ph14020110 ◽

2021 ◽

Vol 14 (2) ◽

pp. 110

Author(s):

Caitlin Jie ◽

Valerie Treyer ◽

Roger Schibli ◽

Linjing Mu

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Pet Imaging ◽

Second Generation ◽

Tau Proteins ◽

Tau Pathology ◽

Pet Tracer ◽

Positron Emission ◽

Tau Pet ◽

Target Binding

Tauvid has been approved by the U.S. Food and Drug Administration (FDA) in 2020 for positron emission tomography (PET) imaging of adult patients with cognitive impairments undergoing evaluation for Alzheimer’s disease (AD) based on tau pathology. Abnormal aggregation of tau proteins is one of the main pathologies present in AD and is receiving increasing attention as a diagnostic and therapeutic target. In this review, we summarised the production and quality control of Tauvid, its clinical application, pharmacology and pharmacokinetics, as well as its limitation due to off-target binding. Moreover, a brief overview on the second-generation of Tau PET tracers is provided. The approval of Tauvid marks a step forward in the field of AD research and opens up opportunities for second-generation tau tracers to advance tau PET imaging in the clinic.

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TauIQ - A canonical image based algorithm to quantify tau PET scans

Journal of Nuclear Medicine ◽

10.2967/jnumed.120.258962 ◽

2021 ◽

pp. jnumed.120.258962

Author(s):

Alex Whittington ◽

Roger Gunn

Keyword(s):

Tau Pet ◽

Pet Scans ◽

Canonical Image

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Medial temporal tau can be a predictor for amyloid-ß positivity in mild cognitive impairment

10.21203/rs.3.rs-16213/v1 ◽

2020 ◽

Author(s):

Hanna Cho ◽

Min Seok Baek ◽

Hye Sun Lee ◽

Jae Yong Choi ◽

Jae Hoon Lee ◽

...

Keyword(s):

Area Under The Curve ◽

Standardized Uptake Value ◽

Visual Assessment ◽

Parahippocampal Cortex ◽

Positron Emission ◽

Auc Value ◽

Tau Pet ◽

Sensitivity Specificity ◽

Post Hoc ◽

Pet Scans

Abstract Introduction Although both amyloid-ß (Aß) and tau positron emission tomography (PET) are important for the assessment of Alzheimer’s disease pathology, obtaining two PET scans can be challenging in clinical practice. We sought to determine whether Aß-positivity in MCI patients can be predicted with only a single tau PET scan. Methods We prospectively recruited 105 MCI patients and performed two PET scans with 18 F-florbetaben and 18 F-flortaucipir with all patients. Regional 18 F-flortaucipir standardized uptake value ratios (SUVR) were measured using FreeSurfer-generated volumes-of-interest and with the cerebellar crus median as a reference. Results We classified 49 (46.7%) MCI patients as Aß-positive using visual assessment. In 12 regions showing greater tau uptake in the MCI-Aβ+ patients compared to the MCI-Aβ- patients, tau uptake in the entorhinal cortex showed the greatest area under the curve (AUC) value (AUC = 0.835, sensitivity/specificity = 73.5% /85.7%) for discriminating Aß-positivity. The second and third largest AUCs were obtained with tau uptake in the amygdala (AUC = 0.814, sensitivity/specificity = 65.3%/94.6%) and the parahippocampal cortex (AUC = 0.802, sensitivity/specificity = 67.4%/91.1%). However, post-hoc analyses revealed no statistical differences between the three regions. Conclusions Single tau PET scans may be helpful in the evaluation of disease state and stage at the same time in MCI patients.

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Amyloid duration is associated with preclinical cognitive decline and tau PET

10.1101/778415 ◽

2019 ◽

Cited By ~ 1

Author(s):

Rebecca L. Koscik ◽

Tobey J. Betthauser ◽

Erin M. Jonaitis ◽

Samantha L. Allison ◽

Lindsay R. Clark ◽

...

Keyword(s):

Cognitive Decline ◽

Neurofibrillary Tangle ◽

Amyloid Pet ◽

Clinical Progression ◽

Amyloid Positron Emission Tomography ◽

Preclinical Ad ◽

Positron Emission ◽

Increased Risk ◽

Tau Pet ◽

Pet Scans

ABSTRACTINTRODUCTIONThis study applies a novel algorithm to longitudinal amyloid positron emission tomography (PET) imaging to identify age-heterogeneous amyloid trajectory groups, estimate the age and duration (chronicity) of amyloid positivity, and investigate chronicity in relation to cognitive decline and tau burden.METHODSCognitively unimpaired participants (n=257) underwent 1-4 amyloid PET scans. Group-based trajectory modeling was applied to participants with longitudinal scans (n=171) to identify and model amyloid trajectory groups, which were combined with Bayes’ theorem to estimate age and chronicity of amyloid positivity. Relationships between chronicity, cognition, clinical progression and tau PET (MK-6240) were investigated using regression models.RESULTSChronicity explained more heterogeneity in amyloid binding than age and binary amyloid status. Chronicity was associated with faster cognitive decline, increased risk of abnormal cognition, and higher entorhinal tau.DISCUSSIONAmyloid chronicity provides unique information about cognitive decline and neurofibrillary tangle development and may be useful to investigate preclinical AD.

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In vivo characterization and quantification of neurofibrillary tau PET radioligand [18F]MK-6240 in humans from Alzheimer’s disease dementia to young controls

10.1101/290064 ◽

2018 ◽

Cited By ~ 3

Author(s):

Tobey J Betthauser ◽

Karly A Cody ◽

Matthew D Zammit ◽

Dhanabalan Murali ◽

Alexander K Converse ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Pet Imaging ◽

Optimal Timing ◽

Reference Tissue ◽

Time Activity ◽

Imaging Characteristics ◽

Tau Pet ◽

Target Binding

ABSTRACTTau positron emission tomography (PET) imaging has potential for elucidating changes in the deposition of neuropathological tau aggregates that are occurring during the progression of Alzheimer’s disease (AD). This work investigatesin vivokinetics, quantification strategies and imaging characteristics of a novel tau PET radioligand [18F]MK-6240 in humans.MethodsFifty-one individuals ranging from cognitively normal young controls to persons with dementia underwent T1-weighted magnetic resonance imaging (MRI), and [11C]PiB and [18F]MK-6240 PET imaging. PET data were coregistered to the MRI and time-activity curves were extracted from regions of interest to assess [18F]MK-6240 kinetics. The pons and inferior cerebellum were investigated as potential reference regions. Reference tissue methods (Logan graphical analysis (LGA) and multilinear reference tissue method (MRTM2)) were investigated for quantification of [18F]MK-6240 distribution volume ratios (DVRs) in a subset of nineteen participants. Stability of DVR methods was evaluated using truncated scan durations. Standard uptake value ratio (SUVR) estimates were compared to DVR estimates to determine the optimal timing window for SUVR analysis. Parametric SUVR images were used to identify regions of potential off-target binding and to compare binding patterns with neurofibrillary tau staging established in neuropathology literature.ResultsStandard uptake values in the pons and the inferior cerebellum indicated consistent clearance across all 51 subjects. LGA and MRTM2 DVR estimates were similar, with LGA slightly underestimating DVR compared to MRTM2. DVR estimates remained stable when truncating the scan duration to 60 minutes. SUVR determined 70-90 minutes post-injection of [18F]MK-6240 indicated linearity near unity when compared to DVR estimates and minimized potential spill-in from uptake outside of the brain. [18F]MK-6240 binding patterns in target regions were consistent with neuropathological neurofibrillary tau staging. Off-target binding regions included the ethmoid sinus, clivus, meninges, substantia nigra, but not the basal ganglia or choroid plexus.Conclusions[18F]MK-6240 is a promising PET radioligand forin vivoimaging of neurofibrillary tau aggregates in AD with minimal off-target binding in the human brain.

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