Head-to-head comparison of tau PET tracers [F]PI-2620 and [F]RO948 in non-demented individuals with brain amyloid deposition: the TAU-PET FACEHBI cohort.

Background: Second-generation tau tracers for positron emission tomography (PET) show high affinity for paired helical filaments tau deposits characteristic of Alzheimer´s disease and low off-target binding. Differences in their chemical structure though may lead to variations in their regional tau uptake and off-target signal. In this work, we aimed to compare the in-vivo uptake of tau tracers [F]PI-2620 and [F]RO948 in the early stages of the AD continuum.

Centiloid recommendations for clinical context-of-use from the AMYPAD consortium.

Amyloid-PET quantification through the tracer-independent Centiloid (CL) scale has emerged as an essential tool for the accurate measurement of amyloid-β (Aβ) pathology in Alzheimer's disease (AD) patients. The AMYPAD consortium set out to integrate existing literature and recent work from the consortium to provide clinical context-of-use recommendations for the CL scale. Compared to histopathology, visual reads, and cerebrospinal fluid, CL quantification accurately reflects the amount of AD pathology.

Qualitative and quantitative analysis of 18F-GP1 positron emission tomography in thrombotic cardiovascular disease.

F-GP1 is a novel highly specific radiotracer that binds to activated platelets and thrombus. We aimed to establish the observer repeatability of coronary, carotid and cerebral F-GP1 uptake in patients presenting with acute myocardial infarction or ischaemic stroke. Forty-three patients presenting with acute myocardial infarction or ischaemic stroke underwent hybrid positron emission tomography (PET) and computed tomography (CT) angiography.

Harmonizing tau positron emission tomography in Alzheimer's disease: The CenTauR scale and the joint propagation model.

Introduction: Tau-positron emission tomography (PET) outcome data of patients with Alzheimer's disease (AD) cannot currently be meaningfully compared or combined when different tracers are used due to differences in tracer properties, instrumentation, and methods of analysis.

Methods: Using head-to-head data from five cohorts with tau PET radiotracers designed to target tau deposition in AD, we tested a joint propagation model (JPM) to harmonize quantification (units termed "CenTauR" [CTR]). JPM is a statistical model that simultaneously models the relationships between head-to-head and anchor point data.

Association Between Years of Education and Amyloid Burden in Patients With Subjective Cognitive Decline, MCI, and Alzheimer Disease.

Objectives: Higher-educated patients with Alzheimer disease (AD) can harbor greater neuropathologic burden than those with less education despite similar symptom severity. In this study, we assessed whether this observation is also present in potential preclinical AD stages, namely in individuals with subjective cognitive decline and clinical features increasing AD likelihood (SCD+).

Methods: Amyloid-PET information ([F]Flutemetamol or [F]Florbetaben) of individuals with SCD+, mild cognitive impairment (MCI), and AD were retrieved from the AMYPAD-DPMS cohort, a multicenter randomized controlled study.

Association of Neurofilament Light Chain, [F]PI-2620 Tau-PET, TSPO-PET, and Clinical Progression in Patients With β-Amyloid-Negative CBS.

Background And Objectives: Corticobasal syndrome (CBS) with underlying 4-repeat tauopathy is a progressive neurodegenerative disease characterized by declining cognitive and motor functions. Biomarkers for assessing pathologic brain changes in CBS including tau-PET, 18 kDa translocator protein (TSPO)-PET, structural MRI, neurofilament light chain (NfL), or glial fibrillary acidic protein (GFAP) have recently been evaluated for differential diagnosis and disease staging, yet their association with disease trajectories remains unclear. Therefore, we performed a head-to-head comparison of neuroimaging (tau-PET, TSPO-PET, structural MRI) and plasma biomarkers (NfL, GFAP) as prognostic tools for longitudinal clinical trajectories in β-amyloid (Aβ)-negative CBS.

Noninvasive In Vivo Thrombus Imaging in Patients With Ischemic Stroke or Transient Ischemic Attack-Brief Report.

Background: F-GP1 is a novel positron-emitting radiotracer that is highly specific for activated platelets and thrombus. In a proof-of-concept study, we aimed to determine its potential clinical application in establishing the role and origin of thrombus in ischemic stroke.

Methods: Eleven patients with recent ischemic stroke (n=9) or transient ischemic attack (n=2) underwent F-GP1 positron emission tomography and computed tomography angiography at a median of 11 (range, 2-21) days from symptom onset.

Validation of quantitative assessment of florbetaben PET scans as an adjunct to the visual assessment across 15 software methods.

Purpose: Amyloid positron emission tomography (PET) with [F]florbetaben (FBB) is an established tool for detecting Aβ deposition in the brain in vivo based on visual assessment of PET scans. Quantitative measures are commonly used in the research context and allow continuous measurement of amyloid burden. The aim of this study was to demonstrate the robustness of FBB PET quantification.

Clinical Effect of Early vs Late Amyloid Positron Emission Tomography in Memory Clinic Patients: The AMYPAD-DPMS Randomized Clinical Trial.

Importance: Amyloid positron emission tomography (PET) allows the direct assessment of amyloid deposition, one of the main hallmarks of Alzheimer disease. However, this technique is currently not widely reimbursed because of the lack of appropriately designed studies demonstrating its clinical effect.

Objective: To assess the clinical effect of amyloid PET in memory clinic patients.

[F]F-DED PET imaging of reactive astrogliosis in neurodegenerative diseases: preclinical proof of concept and first-in-human data.

Objectives: Reactive gliosis is a common pathological hallmark of CNS pathology resulting from neurodegeneration and neuroinflammation. In this study we investigate the capability of a novel monoamine oxidase B (MAO-B) PET ligand to monitor reactive astrogliosis in a transgenic mouse model of Alzheimer`s disease (AD). Furthermore, we performed a pilot study in patients with a range of neurodegenerative and neuroinflammatory conditions.

Analysis of Psychological Symptoms Following Disclosure of Amyloid-Positron Emission Tomography Imaging Results to Adults With Subjective Cognitive Decline.

Importance: Individuals who are amyloid-positive with subjective cognitive decline and clinical features increasing the likelihood of preclinical Alzheimer disease (SCD+) are at higher risk of developing dementia. Some individuals with SCD+ undergo amyloid-positron emission tomography (PET) as part of research studies and frequently wish to know their amyloid status; however, the disclosure of a positive amyloid-PET result might have psychological risks.

Objective: To assess the psychological outcomes of the amyloid-PET result disclosure in individuals with SCD+ and explore which variables are associated with a safer disclosure in individuals who are amyloid positive.

A more precise diagnosis by means of amyloid PET contributes to delayed institutionalization, lower mortality, and reduced care costs in a tertiary memory clinic setting.

Introduction: We aim to study the effect of a more precise diagnosis, by means of amyloid positron emission tomography (PET), on institutionalization, mortality, and health-care costs.

Methods: Between October 27, 2014 and December 31, 2016, we offered amyloid PET to all patients as part of their diagnostic work-up. Patients who accepted to undergo amyloid PET (n = 449) were propensity score matched with patients without amyloid PET (n = 571, i.

Additive value of [F]PI-2620 perfusion imaging in progressive supranuclear palsy and corticobasal syndrome.

Purpose: Early after [F]PI-2620 PET tracer administration, perfusion imaging has potential for regional assessment of neuronal injury in neurodegenerative diseases. This is while standard late-phase [F]PI-2620 tau-PET is able to discriminate the 4-repeat tauopathies progressive supranuclear palsy and corticobasal syndrome (4RTs) from disease controls and healthy controls. Here, we investigated whether early-phase [F]PI-2620 PET has an additive value for biomarker based evaluation of 4RTs.

Value of Ga-labeled bombesin antagonist (RM2) in the detection of primary prostate cancer comparing with [F]fluoromethylcholine PET-CT and multiparametric MRI-a phase I/II study.

Objectives: The bombesin derivative RM2 is a GRPr antagonist with strong binding affinity to prostate cancer (PCa). In this study, the impact of [Ga]Ga-RM2 positron emission tomography-computed tomography (PET-CT) for the detection of primary PCa was compared with that of [F]FCH PET-CT and multiparametric magnetic resonance imaging (mpMRI).

Methods: This phase I/II study was conducted in 30 biopsy-positive PCa subjects.

Description of a European memory clinic cohort undergoing amyloid-PET: The AMYPAD Diagnostic and Patient Management Study.

Introduction: AMYPAD Diagnostic and Patient Management Study (DPMS) aims to investigate the clinical utility and cost-effectiveness of amyloid-PET in Europe. Here we present participants' baseline features and discuss the representativeness of the cohort.

Methods: Participants with subjective cognitive decline plus (SCD+), mild cognitive impairment (MCI), or dementia were recruited in eight European memory clinics from April 16, 2018, to October 30, 2020, and randomized into three arms: ARM1, early amyloid-PET; ARM2, late amyloid-PET; and ARM3, free-choice.

F-PI-2620 Tau PET Improves the Imaging Diagnosis of Progressive Supranuclear Palsy.

Progressive supranuclear palsy (PSP) is a 4-repeat tauopathy movement disorder that can be imaged by the F-labeled tau PET tracer 2-(2-([F]fluoro)pyridin-4-yl)-9-pyrrolo[2,3-:4,5-']dipyridine (F-PI-2620). The in vivo diagnosis is currently established on clinical grounds and supported by midbrain atrophy estimation in structural MRI. Here, we investigate whether F-PI-2620 tau PET has the potential to improve the imaging diagnosis of PSP.

Quantification of amyloid PET for future clinical use: a state-of-the-art review.

Amyloid-β (Aβ) pathology is one of the earliest detectable brain changes in Alzheimer's disease (AD) pathogenesis. The overall load and spatial distribution of brain Aβ can be determined in vivo using positron emission tomography (PET), for which three fluorine-18 labelled radiotracers have been approved for clinical use. In clinical practice, trained readers will categorise scans as either Aβ positive or negative, based on visual inspection.

Multicenter F-PI-2620 PET for In Vivo Braak Staging of Tau Pathology in Alzheimer's Disease.

Tau aggregates accumulate in the Alzheimer's disease (AD) brain according to the established Braak staging scheme and spread from transentorhinal over limbic regions to the neocortex. To impact the management of AD patients, an in vivo tool for tau Braak staging is needed. First-generation tau tracers have limited performance in detecting early stages of tau.

Tau deposition patterns are associated with functional connectivity in primary tauopathies.

Tau pathology is the main driver of neuronal dysfunction in 4-repeat tauopathies, including cortico-basal degeneration and progressive supranuclear palsy. Tau is assumed to spread prion-like across connected neurons, but the mechanisms of tau propagation are largely elusive in 4-repeat tauopathies, characterized not only by neuronal but also by astroglial and oligodendroglial tau accumulation. Here, we assess whether connectivity is associated with 4R-tau deposition patterns by combining resting-state fMRI connectomics with both 2 generation F-PI-2620 tau-PET in 46 patients with clinically diagnosed 4-repeat tauopathies and post-mortem cell-type-specific regional tau assessments from two independent progressive supranuclear palsy patient samples (n = 97 and n = 96).

PET Imaging of System x in Immune Cells for Assessment of Disease Activity in Mice and Patients with Inflammatory Bowel Disease.

We aimed to explore whether the imaging of antiporter system x of immune cells with (4)-4-(3-F-fluoropropyl)-l-glutamate (F-FSPG) PET can assess inflammatory bowel disease (IBD) activity in murine models and patients (NCT03546868). F-FSPG PET imaging was performed to assess IBD activity in mice with dextran sulfate sodium-induced and adoptive T-cell transfer-induced IBD and a cohort of 20 patients at a tertiary care center in South Korea. Immunohistochemical analysis of system x and cell surface markers was also studied.

18F-GP1 Positron Emission Tomography and Bioprosthetic Aortic Valve Thrombus.

Background: Bioprosthetic valve thrombosis may have implications for valve function and durability.

Objectives: Using a novel glycoprotein IIb/IIIa receptor radiotracer 18F-GP1, we investigated whether positron emission tomography (PET)-computed tomography (CT) could detect thrombus formation on bioprosthetic aortic valves.

Methods: Ex vivo experiments were performed on human platelets and explanted bioprosthetic aortic valves.

GMP-Compliant Radiosynthesis of [F]GP1, a Novel PET Tracer for the Detection of Thrombi.

Thrombus formation and thromboembolic events play important roles in various cardiovascular pathologies. The key receptor involved in platelet aggregation is the fibrinogen receptor glycoprotein IIb/IIIa. [F]GP1, a derivative of the GPIIb/IIIa antagonist elarofiban, is a specific F-labeled small-molecule radiotracer that binds with high affinity to GPIIb/IIIa receptors of activated platelets.