Quantification of amyloid PET for future clinical use: a state-of-the-art review
Open accessAbstract
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. Diagnostic decisions are often based on these reads and patient selection for clinical trials is increasingly guided by amyloid status. However, tracer deposition in the grey matter as a function of amyloid load is an inherently continuous process, which is not sufficiently appreciated through binary cut-offs alone. State-of-the-art methods for amyloid PET quantification can generate tracer-independent measures of Aβ burden. Recent research has shown the ability of these quantitative measures to highlight pathological changes at the earliest stages of the AD continuum and generate more sensitive thresholds, as well as improving diagnostic confidence around established binary cut-offs. With the recent FDA approval of aducanumab and more candidate drugs on the horizon, early identification of amyloid burden using quantitative measures is critical for enrolling appropriate subjects to help establish the optimal window for therapeutic intervention and secondary prevention. In addition, quantitative amyloid measurements are used for treatment response monitoring in clinical trials. In clinical settings, large multi-centre studies have shown that amyloid PET results change both diagnosis and patient management and that quantification can accurately predict rates of cognitive decline. Whether these changes in management reflect an improvement in clinical outcomes is yet to be determined and further validation work is required to establish the utility of quantification for supporting treatment endpoint decisions. In this state-of-the-art review, several tools and measures available for amyloid PET quantification are summarised and discussed. Use of these methods is growing both clinically and in the research domain. Concurrently, there is a duty of care to the wider dementia community to increase visibility and understanding of these methods.
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The range from 12 Centiloids to 30 Centiloids has been proposed to reflect the 'gray zone' of Aβ deposition.
“Moreover, the range from 12 Centiloids to 30 Centiloids has been proposed to reflect the ‘gray zone’ of Aβ deposition24.”
From Plasma p-tau231 and p-tau217 as state markers of amyloid-β pathology in preclinical Alzheimer’s disease (2022) · cites this paper as [24]
The Centiloid scaling section says clinical studies have defined “grey zone” patient cut-offs, supporting the general idea. It does not give 12 and 30 Centiloids as the boundaries of that zone; the section instead mentions other thresholds, including an intermediate range of 20–40 CL for a clinical trial. No page number is available in our copy. (LLM, conf=0.86)
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“The CL scale has been used in clinical trial settings to track therapy response measure [111–114, 159, 160], determine strategies for reducing AD prevention trial sample sizes [161], and improve patient selection for trials [48, 162] and could assist in treatment endpoint decisions [51].”
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Hippocampal Sclerosis Detection with NeuroQuant Compared with Neuroradiologists
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Amyloid PET Quantification Via End-to-End Training of a Deep Learning
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Self-citationA Retrospective Belgian Multi-Center MRI Biomarker Study in Alzheimer’s Disease (REMEMBER)
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Standardized Uptake Value Ratio-Independent Evaluation of Brain Amyloidosis
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Quantifying eloquent locations for glioblastoma surgery using resection probability maps
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Amyloid and APOE Status of Screened Subjects in the Elenbecestat MissionAD Phase 3 Program
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PET amyloid in normal aging: direct comparison of visual and automatic processing methods
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Toward a Universal Readout for18F-Labeled Amyloid Tracers: The CAPTAINs Study
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Considerations for Performing Level-2 Centiloid Transformations for Amyloid PET SUVR values
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Self-citationClinical evaluation of automated quantitative MRI reports for assessment of hippocampal sclerosis
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Parametric imaging of dual-time window [18F]flutemetamol and [18F]florbetaben studies
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Self-citationQuantitative appraisal of the Amyloid Imaging Taskforce appropriate use criteria for amyloid‐PET
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Self-citationAlzheimer's disease drug development pipeline: 2025
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Amyloid-β and Phosphorylated Tau are the Key Biomarkers and Predictors of Alzheimer’s Disease
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Plasma Phosphorylated Tau 217 to Identify Preclinical Alzheimer Disease
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The Future of (Radio)‐Labeled Compounds in Research and Development within the Life Science Industry
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- Authors
- Pemberton, H. G., Collij, L. E., Heeman, F., Bollack, A., Shekari, M., Salvadó, G., Alves, I. L., Garcia, D. V., Battle, M., Buckley, C., Stephens, A. W., Bullich, S., Garibotto, V., Barkhof, F., Gispert, J. D., Farrar, G., & on behalf of the AMYPAD consortium
- Affiliations
- UCL Queen Square Institute of Neurology (GB)
- Amsterdam University Medical Centers (NL)
- University College London (GB)
- Universitat Pompeu Fabra (ES)
- Lund University (SE)
- University of Geneva (CH)
- Corresponding author
- Pemberton, Hugh G.
- ORCID
- Venue
- European Journal of Nuclear Medicine and Molecular Imaging
- Published
- 2022-04-07
- Volume
- 49
- Issue
- 10
- Pages
- 3508-3528
- ISSN
- 1619-7070 (ISSN-L)
- 1619-7089
- PMC
- PMC9308604
- OpenAlex
- W4225623397
- Cited by
- 226
- References
- 220
- Citations by year
- 2026: 61 · 2025: 71 · 2024: 64 · 2023: 25 · 2022: 5
- FWCI
- 7.10
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- European Journal of Nuclear Medicine and Molecular Imaging (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion, other-oa)
- Archive ouverte UNIGE (University of Geneva) (publishedVersion, other-oa)
- Pure Amsterdam UMC (submittedVersion, cc-by)
- UCL Discovery (University College London) (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Repositori digital de la UPF (Universitat Pompeu Fabra) (submittedVersion, cc-by)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- Innovative Medicines Initiative (115952)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
- Keywords
- amyloid PET quantification, amyloid-beta, Alzheimer's disease, fluorine-18 radiotracer, aducanumab, treatment response monitoring, cognitive decline prediction, patient selection for clinical trials, amyloid imaging
- MeSH terms
- Alzheimer Disease, Amyloid, Amyloidosis, Brain, Humans, Amyloid beta-Peptides, Positron-Emission Tomography, Cognitive Dysfunction
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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