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.

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.

Stress testing the Centiloid: Precision and variability of PET quantification of amyloid pathology.

Introduction: Assessing the potential sources of bias and variability of the Centiloid (CL) scale is fundamental for its appropriate clinical application.

Methods: We included 533 participants from AMYloid imaging to Prevent Alzheimer's Disease (AMYPAD DPMS) and Alzheimer's Disease Neuroimaging Initiative (ADNI) cohorts. Thirty-two CL pipelines were created using different combinations of reference region (RR), RR and target types, and quantification spaces.

CenTauR: Toward a universal scale and masks for standardizing tau imaging studies.

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.

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.

Quantification of [ F]florbetaben amyloid-PET imaging in a mixed memory clinic population: The ABIDE project.

Introduction: We investigated amyloid-burden quantification in a mixed memory clinic population.

Methods: [ F]Florbetaben amyloid-PET (positron emission tomography) scans of 348 patients were visually read and quantified using the Centiloid (CL) method. General linear models were used to assess CL differences across syndromic and etiological diagnosis.

Evaluation of tau deposition using F-PI-2620 PET in MCI and early AD subjects-a MissionAD tau sub-study.

Background: The ability of F-PI-2620 PET to measure the spatial distribution of tau pathology in Alzheimer's disease (AD) has been demonstrated in previous studies. The objective of this work was to evaluate tau deposition using F-PI-2620 PET in beta-amyloid positive subjects with a diagnosis of mild cognitive impairment (MCI) or mild AD dementia and characterize it with respect to amyloid deposition, cerebrospinal fluid (CSF) assessment, hippocampal volume, and cognition.

Methods: Subjects with a diagnosis of MCI due to AD or mild AD dementia and a visually amyloid-positive F-florbetaben PET scan (n=74, 76 ± 7 years, 38 females) underwent a baseline F-PI-2620 PET, T1-weighted magnetic resonance imaging (MRI), CSF assessment (Aβ42/Aβ40 ratio, p-tau, t-tau) (n=22) and several cognitive tests.

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.

Validation of amyloid PET positivity thresholds in centiloids: a multisite PET study approach.

Background: Inconsistent positivity thresholds, image analysis pipelines, and quantitative outcomes are key challenges of multisite studies using more than one β-amyloid (Aβ) radiotracer in positron emission tomography (PET). Variability related to these factors contributes to disagreement and lack of replicability in research and clinical trials. To address these problems and promote Aβ PET harmonization, we used [F]florbetaben (FBB) and [F]florbetapir (FBP) data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) to derive (1) standardized Centiloid (CL) transformations and (2) internally consistent positivity thresholds based on separate young control samples.

Early detection of amyloid load using F-florbetaben PET.

Background: A low amount and extent of Aβ deposition at early stages of Alzheimer's disease (AD) may limit the use of previously developed pathology-proven composite SUVR cutoffs. This study aims to characterize the population with earliest abnormal Aβ accumulation using F-florbetaben PET. Quantitative thresholds for the early (SUVR) and established (SUVR) Aβ deposition were developed, and the topography of early Aβ deposition was assessed.

Validation of a spatial normalization method using a principal component derived adaptive template for [F]florbetaben PET.

Quantification may help in the context of amyloid-β positron emission tomography (PET). Quantification typically requires that PET images be spatially normalized, a process that can be subject to bias. We herein aimed to test whether a principal component approach (PCA) previously applied to [F]flutemetamol PET extends to [F]florbetaben.

Initial evaluation of (4S)-4-(3-[F]fluoropropyl)-L-glutamate (FSPG) PET/CT imaging in patients with head and neck cancer, colorectal cancer, or non-Hodgkin lymphoma.

Purpose: (4S)-4-(3-[F]Fluoropropyl)-L-glutamic acid ([F]FSPG) measures system x transporter activity and shows promise for oncologic imaging. We present data on tumor uptake of this radiopharmaceutical in human subjects with head and neck cancer (HNC), colorectal cancer (CRC), and non-Hodgkin lymphoma (NHL).

Methods: A total of 15 subjects with HNC (n = 5), CRC (n = 5), or NHL (n = 5) were recruited (mean age 66.

Clinical Evaluation of (4S)-4-(3-[F]Fluoropropyl)-L-glutamate (F-FSPG) for PET/CT Imaging in Patients with Newly Diagnosed and Recurrent Prostate Cancer.

Purpose: (4S)-4-(3-[F]Fluoropropyl)--glutamic acid (F-FSPG) is a radiopharmaceutical for PET imaging of system x activity, which can be upregulated in prostate cancer. We present data on the first evaluation of patients with newly diagnosed or recurrent prostate cancer with this radiopharmaceutical.

Experimental Design: Ten patients with primary and 10 patients with recurrent prostate cancer were enrolled in this prospective multicenter study.

Simulating the effect of cerebral blood flow changes on regional quantification of [F]flutemetamol and [F]florbetaben studies.

Global and regional changes in cerebral blood flow (CBF) can result in biased quantitative estimates of amyloid load by PET imaging. Therefore, the current simulation study assessed effects of these changes on amyloid quantification using a reference tissue approach for [F]flutemetamol and [F]florbetaben. Previously validated pharmacokinetic rate constants were used to simulate time-activity curves (TACs) corresponding to full dynamic and dual-time-window acquisition protocols.

Evaluation of Dosimetry, Quantitative Methods, and Test-Retest Variability of F-PI-2620 PET for the Assessment of Tau Deposits in the Human Brain.

F-PI-2620 is a next-generation tau PET tracer that has demonstrated ability to image the spatial distribution of suspected tau pathology. The objective of this study was to assess the tracer biodistribution, dosimetry, and quantitative methods of F-PI-2620 in the human brain. Full kinetic modeling to quantify tau load was investigated.

Tau PET imaging with F-PI-2620 in Patients with Alzheimer Disease and Healthy Controls: A First-in-Humans Study.

F-PI-2620 is a PET tracer with high binding affinity for aggregated tau, a key pathologic feature of Alzheimer disease (AD) and other neurodegenerative disorders. Preclinically, F-PI-2620 binds to both 3-repeat and 4-repeat tau isoforms. The purpose of this first-in-humans study was to evaluate the ability of F-PI-2620 to detect tau pathology in AD patients using PET imaging, as well as to assess the safety and tolerability of this new tau PET tracer.

Comparison of F-florbetaben quantification results using the standard Centiloid, MR-based, and MR-less CapAIBL approaches: Validation against histopathology.

Introduction: F-florbetaben is currently approved for the visual rule out of β-amyloid (Aβ) pathology. It is also used for recruitment and as an outcome measure in therapeutic trials, requiring accurate and reproducible quantification of Aβ burden in the brain.

Methods: Data from eighty-eight subjects (52 male subjects, aged 79.

Optimized dual-time-window protocols for quantitative [F]flutemetamol and [F]florbetaben PET studies.

Background: A long dynamic scanning protocol may be required to accurately measure longitudinal changes in amyloid load. However, such a protocol results in a lower patient comfort and scanning efficiency compared to static scans. A compromise can be achieved by implementing dual-time-window protocols.

Validation of Noninvasive Tracer Kinetic Analysis of F-Florbetaben PET Using a Dual-Time-Window Acquisition Protocol.

Accurate amyloid PET quantification is necessary for monitoring amyloid-β accumulation and response to therapy. Currently, most of the studies are analyzed using the static SUV ratio (SUVR) approach because of its simplicity. However, this approach may be influenced by changes in cerebral blood flow (CBF) or radiotracer clearance.

Added value of F-florbetaben amyloid PET in the diagnostic workup of most complex patients with dementia in France: A naturalistic study.

Introduction: Although some studies have previously addressed the clinical impact of amyloid positron emission tomography (PET), none has specifically addressed its selective and hierarchical implementation in relation to cerebrospinal fluid analysis in a naturalistic setting.

Methods: This multicenter study was performed at French tertiary memory clinics in patients presenting with most complex clinical situations (i.e.

F-Florbetaben PET beta-amyloid binding expressed in Centiloids.

Purpose: The Centiloid (CL) method enables quantitative values from Aβ-amyloid (Aβ) imaging to be expressed in a universal unit providing pathological, diagnostic and prognostic thresholds in clinical practice and research and allowing integration of multiple tracers and methods. The method was developed for C-PiB scans with zero CL set as the average in young normal subjects and 100 CL the average in subjects with mild Alzheimer's disease (AD). The method allows derivation of equations to convert the uptake value of any tracer into the same standard CL units but first requires head-to-head comparison with C-PiB results.

Optimized classification of F-Florbetaben PET scans as positive and negative using an SUVR quantitative approach and comparison to visual assessment.

Introduction: Standardized uptake value ratios (SUVRs) calculated from cerebral cortical areas can be used to categorize F-Florbetaben (FBB) PET scans by applying appropriate cutoffs. The objective of this work was first to generate FBB SUVR cutoffs using visual assessment (VA) as standard of truth (SoT) for a number of reference regions (RR) (cerebellar gray matter (GCER), whole cerebellum (WCER), pons (PONS), and subcortical white matter (SWM)). Secondly, to validate the FBB PET scan categorization performed by SUVR cutoffs against the categorization made by post-mortem histopathological confirmation of the Aβ presence.

Optimal Reference Region to Measure Longitudinal Amyloid-β Change with F-Florbetaben PET.

Accurate measurement of changes in amyloid-β (Aβ) deposition over time is important in longitudinal studies, particularly in anti-Aβ therapeutic trials. To achieve this, the optimal reference region (RR) must be selected to reduce variance of Aβ PET measurements, allowing early detection of treatment efficacy. The aim of this study was to determine the RR that allows earlier detection of subtle Aβ changes using F-florbetaben PET.