Amyloid Imaging

Jagust, William J.

doi:10.1001/archneurol.2011.152

Cited by 9 publications

(10 citation statements)

References 11 publications

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“…The relative sensitivities and specificities of the compounds for detecting and quantifying different levels of Aβ loads in human subjects remain an area of active investigation. 74,85–87 …”

Section: F-labeled Aβ Imaging Agentsmentioning

confidence: 99%

Development of Positron Emission Tomography β-Amyloid Plaque Imaging Agents

Mathis

Mason

Lopresti

et al. 2012

Seminars in Nuclear Medicine

156

111

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For 100 years, β-amyloid (Aβ) plaques and neurofibrillary tangles (NFTs) have been recognized as the neuropathological hallmarks of Alzheimer’s disease (AD), and their presence or absence could only be assessed postmortem using stains and dyes that identified these microscopic structures. Approximately 10 years ago, the first successful Aβ plaque–specific positron emission tomography (PET) imaging study was conducted in a living human subject clinically diagnosed with probable AD using the 11C-labeled radiopharmaceutical Pittsburgh Compound B (PiB). Laboratory studies and preclinical evaluations to design PiB began a decade earlier than the first human PiB PET study and involved chemical modifications of different well-known dyes that bound specifically to the extended β-pleated sheets that comprise the fibrils of amyloid proteins such as Aβ plaques, NFTs, β-synuclein deposits, and prions. These preclinical studies were conducted in our laboratories at the University of Pittsburgh, starting with Congo red derivatives, followed by Chrysamine G derivatives, followed by X-series compounds, and finally with neutral derivatives of thioflavin-T. The in vitro and in vivo evaluations of the different derivatives as candidate PET radioligands for imaging Aβ plaques and neurofibrillary tangles in human brain are described in this review, along with the specific evaluation criteria by which the candidate radioligands were judged. Out of these studies came PiB, a PET radioligand that binds selectively and with high affinity to only fibrillar forms of Aβ. PiB has been used in many different human research protocols throughout the world and has demonstrated the usefulness of assessing the Aβ plaque status of subjects many years before the clinical diagnosis of probable AD. Recently, longer-lived 18F-radiolabeled Aβ-selective radiopharmaceuticals have been developed. It is likely that the full clinical impact of these imaging agents will be realized by identifying presymptomatic subjects who would benefit from early drug treatments with future disease-modifying AD therapeutics.

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Section: F-labeled Aβ Imaging Agentsmentioning

confidence: 99%

Development of Positron Emission Tomography β-Amyloid Plaque Imaging Agents

Mathis

Mason

Lopresti

et al. 2012

Seminars in Nuclear Medicine

156

111

View full text Add to dashboard Cite

show abstract

“…Overall, participants from the 18 F-GTP1 and 18 F-PM-PBB3 cohorts were significantly younger compared to participants from the other cohorts. Compared to the MCI and AD dementia groups, CU Aβ+ participants were significantly older (F-stat=3.9, p<0.002) and had fewer males (F-stat=3, p<0.005).…”

Section: Resultsmentioning

confidence: 87%

“…78 18 F -MK6240 AD Aβ+ scans from the AIBL cohort were visually were visually rated by two readers (CCR and NK), blind to participant characteristics, resulting in consensus visual reads, as previously described [31]. Briefly, scans were rated as i) tau negative (no tracer retention or minimal (unilateral or bilateral) entorhinal cortex retention; ii) limbic predominant (pronounced tracer retention in the MTL with no cortical retention); iii) hippocampal sparing (cortical tau tracer retention with no or minimal MTL signal); or iv) typical (MTL and cortical tracer retention).…”

Section: Visual Subtype Classificationmentioning

confidence: 99%

“…23 scans (eight 18 F-RO948, one 18 F-GTP1, five 18 F-PI2620, one 18 F-FTP, eight 18 F-PM-PBB3) did not pass visual QC using the SPM pipeline or did not have an MRI of sufficient quality while only one scan did not pass visual QC when using both CapAIBL and SPM. A further six CU Aβ-were visually excluded due to the presence of tracer uptake in the MTL.…”

Section: Tau Mask Samplingmentioning

confidence: 99%

“…In the present study, we aimed to standardize tau PET results by establishing the location and amount of abnormality of tau aggregates in the brain, and expressing them in a universal standard scale, the units of which are termed "CenTauRs"-using tau PET data from the six most commonly used tracers ( 18 F-floraucipir, 18 F-MK6240, 18 F-PI2620, 18 F-PM-PBB3, 18 F-RO948, and 18 F-GTP1) and an approach similar to the one used in the Centiloid project.…”

Section: Introductionmentioning

confidence: 99%

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CenTauR: Towards a Universal Scale and Masks for Standardizing Tau Imaging Studies

Villemagne

Leuzy

Bohórquez³

et al. 2023

Preprint

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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: 1045 participants underwent tau scans with either 18F-Flortaucipir, 18F-MK6240, 18F-PI2620, 18F-PM-PBB3, 18F-GTP1 or 18F-RO948. The mask was generated from cognitively unimpaired Aβ- subjects and AD patients with Aβ+. Four additional regional cortical masks were defined within the constraints of the global 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 robustly 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 centres.

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

Villemagne

Leuzy

Bohórquez³

et al. 2023

Alz & Dem Diag Ass & Dis Mo

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INTRODUCTIONRecently, 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.METHODOne 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.RESULTSNone 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.DISCUSSIONWe 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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Amyloid Imaging

Cited by 9 publications

References 11 publications

Development of Positron Emission Tomography β-Amyloid Plaque Imaging Agents

Development of Positron Emission Tomography β-Amyloid Plaque Imaging Agents

CenTauR: Towards a Universal Scale and Masks for Standardizing Tau Imaging Studies

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

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