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[(18)F]flutemetamol amyloid positron emission tomography in preclinical and symptomatic Alzheimer's disease: Specific detection of advanced phases of amyloid-β pathology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. (Nuklearmedicin och PET)
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2015 (English)In: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 11, no 8, 975-85 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Amyloid positron emission tomography (PET) has become an important tool to identify amyloid-β (Aβ) pathology in Alzheimer's disease (AD) patients. Here, we determined the diagnostic value of the amyloid PET tracer [(18)F]flutemetamol in relation to Aβ pathology at autopsy.

METHODS: [(18)F]flutemetamol PET was carried out in a cohort of 68 patients included in a [(18)F]flutemetamol amyloid PET imaging end-of-life study (GE067-007). At autopsy, AD pathology was determined and Aβ plaque pathology was classified into phases of its regional distribution (0-5).

RESULTS: [(18)F]flutemetamol PET was universally positive in cases with advanced stage postmortem Aβ pathology (Aβ phases 4 and 5). Negative amyloid PET was universally observed in nondemented or non-AD dementia cases with initial Aβ phases 1 and 2, whereas 33.3% of the phase 3 cases were positive.

CONCLUSIONS: [(18)F]flutemetamol amyloid PET detects primarily advanced stages of Aβ pathology in preclinical and symptomatic AD cases.

Place, publisher, year, edition, pages
2015. Vol. 11, no 8, 975-85 p.
National Category
Radiology, Nuclear Medicine and Medical Imaging
URN: urn:nbn:se:uu:diva-261035DOI: 10.1016/j.jalz.2015.05.018ISI: 000360912300009PubMedID: 26141264OAI: diva2:849542
Available from: 2015-08-28 Created: 2015-08-28 Last updated: 2015-11-10Bibliographically approved
In thesis
1. Characterization of [18F]flutemetamol binding properties: A β-amyloid PET imaging ligand
Open this publication in new window or tab >>Characterization of [18F]flutemetamol binding properties: A β-amyloid PET imaging ligand
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The criteria for diagnosing Alzheimer’s disease (AD) have recently been revised to include the use of biomarkers for the in vivo presence of β-amyloid, one of the neuropathological hallmarks of AD. Examples of such biomarkers are positron emission tomography (PET) β-amyloid specific ligands, including [18F]flutemetamol. The aim of this thesis was to characterize the binding properties of [18F]flutemetamol from a tracer kinetic perspective as well as by validating binding measures through comparison with tissue pathology assessments. The applicability of previously developed kinetic models of tracer binding for voxel-based analysis was examined and compared to arterial input compartment modelling, the “gold standard” for PET quantification. Several voxel-based methods were found to exhibit high correlations with compartment modelling, including the semi-quantitative standardized uptake value ratio (SUVR). The kinetic components of [18F]flutemetamol uptake were also investigated without model assumptions using the data driven method spectral analysis, with binding to β-amyloid shown to relate to a slow kinetic component. The same component was also found to predominate in the uptake of white matter, known to be free of β-amyloid accumulation. White matter uptake was however possible to separate from β-amyloid binding based on the relative contribution of the slow component to the total volume of distribution. Uptake of [18F]flutemetamol as quantified using SUVR or assessed visually was found to correlate well with tissue pathology assessments. Classifying the brains of 68 deceased subjects who had undergone [18F]flutemetamol PET scanning ante mortem, based on the spatial distribution of β-amyloid according to pre-defined phases, revealed that abnormal uptake patterns of [18F]flutemetamol were only certain to be found in the last phase of β-amyloid accumulation. In the same cohort however, [18F]flutemetamol was also shown to accurately distinguish between subjects with AD and non-AD dementia. While this supports the use of [18F]flutemetamol in clinical settings for ruling out AD, the association of abnormal [18F]flutemetamol uptake to late phases of β-amyloid accumulation may limit the detection of early accumulation and pre-clinical stages of AD. It remains to be investigated whether application of voxel-based methods and slow component filtering may increase sensitivity, particularly in the context of clinical trials.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2015. 74 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1139
Positron emission tomography (PET), molecular imaging, amyloid, tracer validation
National Category
Radiology, Nuclear Medicine and Medical Imaging
Research subject
urn:nbn:se:uu:diva-262019 (URN)978-91-554-9356-1 (ISBN)
Public defence
2015-11-19, Skoogsalen, Akademiska Sjukhuset, Ingång 79, Uppsala, 09:15 (English)
Available from: 2015-10-28 Created: 2015-09-07 Last updated: 2015-11-10

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