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An exploratory efficacy study of the amyloid imaging agent [F-18]flutemetamol in Japanese Subjects
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2015 (English)In: Annals of Nuclear Medicine, ISSN 0914-7187, E-ISSN 1864-6433, Vol. 29, no 5, 391-399 p.Article in journal (Refereed) Published
Abstract [en]

The aim of the study presented was to investigate the brain uptake properties of the amyloid PET agent [F-18]flutemetamol in Japanese healthy controls and clinically probable Alzheimer's disease (AD) patients, and to make a comparison with the results of a previously performed study on Caucasian subjects. [F-18]flutemetamol was recently approved by the American Food and Drug Administration and the European Medicines Agency for visualization of amyloid in vivo. Since the first clinical study of [F-18]flutemetamol-an F-18 derivative of the PET tracer 11C-Pittsburgh Compound B targeting beta-amyloid--took place, several clinical studies have been performed, but few focusing on a Japanese population. In the Step A, three elderly healthy volunteers and three AD subjects underwent dynamic PET scanning 0-30 and 60-150 min after injection of 185 MBq [F-18]flutemetamol. The brain volume of distribution (V-T) was quantified using Logan's linear graphical analysis and as standardized uptake value ratios (SUVR) with a cerebellar reference. The optimal acquisition window was determined from brain time activity curves for Step B. In the Step B, 5 AD and 5 elderly healthy volunteers were scanned from 80 to 140 min after intravenous injection of [F-18]flutemetamol. The data from the two parts were pooled for estimation of overall efficacy. [F-18]Flutemetamol injection was shown to be safe-no serious adverse events were reported during this study. A simplified SUVR estimate of the uptake of [F-18]flutemetamol using a time window of 85-115 min post injection successfully discriminated AD cases from healthy volunteers. AD subjects showed an elevated tracer uptake in prefrontal cortex, the lateral temporal cortex and precuneus amongst other regions. No significant [F-18]flutemetamol PET differences could be seen between the Japanese AD cases in this study and those from an earlier Caucasian study, or between control subjects in Japanese and Caucasian studies. This study supports the use of [F-18]flutemetamol PET in Japanese population as a marker of the presence of fibrillar beta-amyloid. The lack of differences between the Japanese cohort and those from a previous Caucasian cohort supports the extrapolation of results from other Caucasian [F-18]flutemetamol PET studies to the Japanese population.

Place, publisher, year, edition, pages
2015. Vol. 29, no 5, 391-399 p.
Keyword [en]
[F-18] flutemetamol, Alzheimer's disease, Amyloid beta, Japanese population, Positron emission tomography
National Category
Radiology, Nuclear Medicine and Medical Imaging
URN: urn:nbn:se:uu:diva-258778DOI: 10.1007/s12149-015-0957-7ISI: 000356938000001PubMedID: 25874747OAI: oai:DiVA.org:uu-258778DiVA: diva2:842432
Available from: 2015-07-20 Created: 2015-07-20 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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