| 1. |
- Heurling, Kerstin, et al.
(författare)
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Imaging β-amyloid using [(18)F]flutemetamol positron emission tomography : from dosimetry to clinical diagnosis
- 2016
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 43:2, s. 362-373
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Forskningsöversikt (refereegranskat)abstract
- In Alzheimer's disease (AD), the deposition of β-amyloid (Aβ) is hypothesized to result in a series of secondary neurodegenerative processes, leading ultimately to synaptic dysfunction and neuronal loss. Since the advent of the first Aβ-specific positron emission tomography (PET) ligand, (11)C-Pittsburgh compound B ([(11)C]PIB), several (18)F ligands have been developed that circumvent the limitations of [(11)C]PIB tied to its short half-life. To date, three such compounds have been approved for clinical use by the US and European regulatory bodies, including [(18)F]AV-45 ([(18)F]florbetapir; Amyvid™), [(18)F]-BAY94-9172 ([(18)F]florbetaben; Neuraceq™) and [(18)F]3'-F-PIB ([(18)F]flutemetamol; Vizamyl™). The present review aims to summarize and discuss the currently available knowledge on [(18)F]flutemetamol PET. As the (18)F analogue of [(11)C]PIB, [(18)F]flutemetamol may be of use in the differentiation of AD from related neurodegenerative disorders and may help with subject selection and measurement of target engagement in the context of clinical trials testing anti-amyloid therapeutics. We will also discuss its potential use in non-AD amyloidopathies.
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| 2. |
- Heurling, Kerstin, et al.
(författare)
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Synaptic vesicle protein 2A as a potential biomarker in synaptopathies
- 2019
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Ingår i: Molecular and Cellular Neuroscience. - : Elsevier. - 1044-7431 .- 1095-9327. ; 97, s. 34-42
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Tidskriftsartikel (refereegranskat)abstract
- Measuring synaptic density in vivo using positron emission tomography (PET) imaging-based biomarkers targeting the synaptic vesicle protein 2A (SV2A) has received much attention recently due to its potential research and clinical applications in synaptopathies, including neurodegenerative and psychiatric diseases. Fluid-based biomarkers in proteinopathies have previously been suggested to provide information on pathology and disease status that is complementary to PET-based measures, and the same can be hypothesized with respect to SV2A. This review provides an overview of the current state of SV2A PET imaging as a biomarker of synaptic density, the potential role of fluid-based biomarkers for SV2A, and related future perspectives.
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| 3. |
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| 4. |
- Jonasson, My, et al.
(författare)
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Optimal timing of tau pathology imaging and automatic extraction of a reference region using dynamic [18F]THK5317 PET
- 2019
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Ingår i: NeuroImage. - : Elsevier BV. - 2213-1582. ; 22
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Tidskriftsartikel (refereegranskat)abstract
- [F-18]THK5317 is a PET tracer for in-vivo imaging of tau associated with Alzheimer's disease (AD). This work aimed to evaluate optimal timing for standardized uptake value ratio (SUVR) measures with [F-18]THK5317 and automated generation of SUVR-1 and relative cerebral blood flow (R-1) parametric images. Nine AD patients and nine controls underwent 90 min [F-18]THK5317 scans. SUVR-1 was calculated at transient equilibrium (TE) and for seven different 20 min intervals and compared with distribution volume ratio (DVR; reference Logan). Cerebellar grey matter (MRI) was used as reference region. A supervised cluster analysis (SVCA) method was implemented to automatically generate a reference region, directly from the dynamic PET volume without the need of a structural MRI scan, for computation of SUVR-1 and R-1 images for a scan duration matching the optimal timing. TE was reached first in putamen, frontal- and parietal cortex at 22 +/- 4 min for AD patients and in putamen at 20 +/- 0 min in controls. Over all regions and subjects, SUVR20-40-1 correlated best with DVR-1, R-2 = 0.97. High correlation was found between values generated using MRI- and SVCA-based reference (R-2 = 0.93 for SUVR20-40-1; R-2 = 0.94 for R-1). SUVR20-40 allows for accurate semi-quantitative assessment of tau pathology and SVCA may be used to obtain a reference region for calculation of both SUVR-1 and R-1 with 40 min scan duration.
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| 5. |
- Leuzy, Antoine, et al.
(författare)
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Clinical impact of [18F]flutemetamol PET among memory clinic patients with an unclear diagnosis.
- 2019
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 46:6, s. 1276-1286
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To investigate the impact of amyloid PET with [18F]flutemetamol on diagnosis and treatment management in a cohort of patients attending a tertiary memory clinic in whom, despite extensive cognitive assessment including neuropsychological testing, structural imaging, CSF biomarker analysis and in some cases [18F]FDG PET, the diagnosis remained unclear.METHODS: The study population consisted of 207 patients with a clinical diagnosis prior to [18F]flutemetamol PET including mild cognitive impairment (MCI; n = 131), Alzheimer's disease (AD; n = 41), non-AD (n = 10), dementia not otherwise specified (dementia NOS; n = 20) and subjective cognitive decline (SCD; n = 5).RESULTS: Amyloid positivity was found in 53% of MCI, 68% of AD, 20% of non-AD, 20% of dementia NOS, and 60% of SCD patients. [18F]Flutemetamol PET led, overall, to a change in diagnosis in 92 of the 207 patients (44%). A high percentage of patients with a change in diagnosis was observed in the MCI group (n = 67, 51%) and in the dementia NOS group (n = 11; 55%), followed by the non-AD and AD (30% and 20%, respectively). A significant increase in cholinesterase inhibitor treatment was observed after [18F]flutemetamol PET (+218%, 34 patients before and 108 patients after).CONCLUSION: The present study lends support to the clinical value of amyloid PET in patients with an uncertain diagnosis in the tertiary memory clinic setting.
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| 6. |
- Leuzy, Antoine, et al.
(författare)
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Concordance and Diagnostic Accuracy of [C-11]PIB PET and Cerebrospinal Fluid Biomarkers in a Sample of Patients with Mild Cognitive Impairment and Alzheimer's Disease
- 2015
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 45:4, s. 1077-1088
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alzheimer's disease (AD) pathology can be quantified in vivo using cerebrospinal fluid (CSF) levels of amyloid-beta(1-42) (A beta(1-42)), total-tau (t-tau), and phosphorylated tau (p- tau(181p)), as well as with positron emission tomography (PET) using [C-11]Pittsburgh compound-B ([C-11]PIB). Studies assessing concordance between these measures, however, have provided conflicting results. Moreover, it has been proposed that [C-11]PIB PET may be of greater clinical utility in terms of identifying patients with mild cognitive impairment (MCI) who will progress to the dementia phase of AD. Objective: To determine concordance and classification accuracy of CSF biomarkers and [C-11]PIB PET in a cohort of patients with MCI and AD. Methods: 68 patients (MCI, n = 33; AD, n = 35) underwent [C-11]PIB PET and CSF sampling. Cutoffs of >1.41 ([C-11]PIB), <450 pg/mL-and a more lenient cutoff of 550 pg/mL-(A beta(1-42)), <6.5 (A beta(1-42)/p-tau181p), and 1.14 (A beta(1- 42)/t-tau), were used to determine concordance. Logistic regression was used to determine classification accuracy with respect to stable MCI (sMCI) versus MCI who progressed to AD (pMCI). Results: Concordance between [C-11]PIB and A beta(1-42) was highest for sMCI (67%), followed by AD (60%) and pMCI (33%). Agreement was increased across groups using A beta(1-42) < 550 pg/mL, or A beta(1-42) to tau ratios. Logistic regression showed that classification accuracy of [11C] PIB, between sMCI and pMCI, was superior to A beta(1-42) (73% versus 58%), A beta(1-42)/t-tau (63%), and A beta(1-42)/p-tau181p (65%). Conclusion: In the present study, [C-11]PIB proved a better predictor of progression to AD in patients with MCI, relative to CSF measures of A beta(1-42) or A beta(1-42)/tau. Discordance between PET and CSF markers for A beta(1-42) suggests they cannot be used interchangeably, as is currently the case.
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| 7. |
- Leuzy, Antoine, et al.
(författare)
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Derivation and utility of an A beta-PET pathology accumulation index to estimate A beta load
- 2020
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Ingår i: Neurology. - : LIPPINCOTT WILLIAMS & WILKINS. - 0028-3878 .- 1526-632X. ; 95:21, s. E2834-E2844
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Tidskriftsartikel (refereegranskat)abstract
- Objective To evaluate a novel beta-amyloid (A beta)-PET-based quantitative measure (A beta accumulation index [A beta index]), including the assessment of its ability to discriminate between participants based on A beta status using visual read, CSF A beta(42)/A beta(40), and post-mortem neuritic plaque burden as standards of truth. Methods One thousand one hundred twenty-one participants (with and without cognitive impairment) were scanned with A beta-PET: Swedish BioFINDER, n = 392, [F-18]flutemetamol; Alzheimer's Disease Neuroimaging Initiative (ADNI), n = 692, [F-18]florbetapir; and a phase 3 end-of-life study, n = 100, [F-18] flutemetamol. The relationships between A beta index and standardized uptake values ratios (SUVR) from A beta-PET were assessed. The diagnostic performances of A beta index and SUVR were compared with visual reads, CSF A beta(42)/A beta(40), and A beta histopathology used as reference standards. Results Strong associations were observed between A beta index and SUVR (R-2: BioFINDER 0.951, ADNI 0.943, end-of-life, 0.916). Both measures performed equally well in differentiating A beta-positive from A beta-negative participants, with areas under the curve (AUCs) of 0.979 to 0.991 to detect abnormal visual reads, AUCs of 0.961 to 0.966 to detect abnormal CSF A beta(42)/A beta(40), and AUCs of 0.820 to 0.823 to detect abnormal A beta histopathology. Both measures also showed a similar distribution across postmortem-based A beta phases (based on anti-A beta 4G8 antibodies). Compared to models using visual read alone, the addition of the A beta index resulted in a significant increase in AUC and a decrease in Akaike information criterion to detect abnormal A beta histopathology. Conclusion The proposed A beta index showed a tight association to SUVR and carries an advantage over the latter in that it does not require the definition of regions of interest or the use of MRI. A beta index may thus prove simpler to implement in clinical settings and may also facilitate the comparison of findings using different A beta-PET tracers. Classification of evidence This study provides Class III evidence that the A beta accumulation index accurately differentiates A beta-positive from A beta-negative participants compared to A beta-PET visual reads, CSF A beta(42)/A beta(40), and A beta histopathology.
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| 8. |
- Leuzy, Antoine, et al.
(författare)
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Longitudinal uncoupling of cerebral perfusion, glucose metabolism, and tau deposition in Alzheimer's disease
- 2018
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 14:5, s. 652-663
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Cross-sectional findings using the tau tracer [F-18] THK5317 (THK5317) have shown that [F-18]fluorodeoxyglucose (FDG) positron emission tomography (PET) data can be approximated using perfusion measures (early-frame standardized uptake value ratio; ratio of tracer delivery in target to reference regions). In this way, a single PET study can provide both functional and molecular information. Methods: We included 16 patients with Alzheimer's disease who completed follow-up THK5317 and FDG studies 17 months after baseline investigations. Linear mixed-effects models and annual percentage change maps were used to examine longitudinal change. Results: Limited spatial overlap was observed between areas showing declines in THK5317 perfusion measures and FDG. Minimal overlap was seen between areas showing functional change and those showing increased retention of THK5317. Discussion: Our findings suggest a spatiotemporal offset between functional changes and tau pathology and a partial uncoupling between perfusion and metabolism, possibly as a function of Alzheimer's disease severity.
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| 9. |
- Leuzy, Antoine, et al.
(författare)
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Use of amyloid PET across the spectrum of Alzheimer's disease : clinical utility and associated ethical issues
- 2014
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Ingår i: Amyloid. - : Informa UK Limited. - 1350-6129 .- 1744-2818. ; 21:3, s. 143-148
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Forskningsöversikt (refereegranskat)abstract
- Recent advances have made possible the in vivo detection of beta-amyloid (Ab) pathology using positron emission tomography. While the gold standard for amyloid imaging, carbon-11 labeled Pittsburgh compound B is increasingly being replaced by fluorine-18 labeled radiopharmaceuticals, with three already approved for clinical use by US and European regulatory bodies. Appropriate use criteria proposed by an amyloid imaging taskforce convened by the Alzheimer's Association and the Society of Nuclear Medicine and Molecular Imaging recommend restricting use of this technology to the evaluation of patients with mild cognitive impairment or atypical dementia syndromes. While use among asymptomatic individuals is currently viewed as inappropriate due prognostic uncertainty, elevated levels of brain Ab among asymptomatic individuals may represent preclinical Alzheimer's disease. Amyloid imaging is likewise expected to play a role in the design of clinical trials. Though preliminary results suggest amyloid imaging to possess clinical utility and cost-effectiveness, both domains have yet to be assessed systematically. As the field moves toward adoption of a pro-disclosure stance for amyloid imaging findings, it is imperative that a broad range of stakeholders be involved to ensure the appropriateness of emerging policies and protocols.
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| 10. |
- Leuzy, Antoine, et al.
(författare)
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Validation of a spatial normalization method using a principal component derived adaptive template for [18F]florbetaben PET
- 2020
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Ingår i: American Journal of Nuclear Medicine and Molecular Imaging. - : E-CENTURY PUBLISHING CORP. - 2160-8407. ; 10:4, s. 161-167
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Tidskriftsartikel (refereegranskat)abstract
- Quantification may help in the context of amyloid-beta 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-18]flutemetamol PET extends to [F-18] florbetaben. PCA was applied to [F-18]florbetaben PET data for 132 subjects (70 Alzheimer dementia, 62 controls) and used to generate an adaptive synthetic template. Spatial normalization of [F-18]florbetaben data using this approach was compared to that achieved using SPM12's magnetic resonance (MR) imaging driven algorithm. The two registration methods showed high agreement and minimal difference in standardized uptake value ratios (SUVR) (R-2 = 0.997 using cerebellum as reference region and 0.996 using the pons). Our method allows for robust and accurate registration of [F-18]florbetaben images to template space, without the need for an MR image, and may prove of value in clinical and research settings.
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