Comparison of 11C-PiB and 18F-florbetaben for Aβ imaging in ageing and Alzheimer’s disease

Villemagne, Victor L.; Mulligan, Rachel; Pejoska, Svetlana; Ong, Kevin; Jones, Gareth; O’Keefe, Graeme; Chan, Janet; Young, Kenneth C.; Tochon-Danguy, Henri; Masters, Colin L.; Rowe, Christopher C.

doi:10.1007/s00259-012-2088-x

Cited by 166 publications

(110 citation statements)

References 33 publications

(48 reference statements)

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“…Likewise, the slope of the linear correlation of 18 F-AZD4694 to 11 C-PiB of 0.95 is higher than those reported for florbetapir (with reported slopes ranging from 0.33 to 0.64) (33,34) and florbetaben (slope of 0.71) (35), and this translates to a wider dynamic range with greater percentage difference between the mean global SUVRs of HCs and AD cohorts and greater image contrast between HC and AD.…”

Section: Discussionmentioning

confidence: 54%

Head-to-Head Comparison of ¹¹C-PiB and ¹⁸F-AZD4694 (NAV4694) for β-Amyloid Imaging in Aging and Dementia

et al. 2013

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11 C-Pittsburgh compound-B ( 11 C-PiB) is the benchmark radiotracer for imaging of b-amyloid (Ab) plaque in Alzheimer disease (AD). 18 F-labeled Ab tracers subsequently developed for clinical use show higher nonspecific white matter binding and, in some cases, lower cortical binding in AD that could lead to less accurate interpretation of scans. We compared the cortical and white matter binding of a new 18 F-labeled Ab tracer, 18 F-AZD4694 (recently renamed NAV4694), with 11 C-PiB in the same subjects. Methods: Forty-five participants underwent PET imaging with 11 C-PiB and 18 F-AZD4694 (25 healthy elderly controls [HCs], 10 subjects with mild cognitive impairment, 7 subjects with probable AD, and 3 subjects with probable frontotemporal dementia). Images were coregistered so that region-ofinterest placement was identical on both scans, and standardized uptake value ratios (SUVRs) using the cerebellar cortex as a reference region were calculated between 40 and 70 min after injection for both tracers. Results: 18 F-AZD4694 showed reversible binding kinetics similar to 11 C-PiB, reaching an apparent steady state at 50 min after injection. Both radiotracers showed a similar dynamic range of neocortical SUVR (1.1-3.3 and 1.0-3.2 SUVR for 11 C-PiB and 18 F-AZD4694, respectively) and identical low nonspecific white matter binding, with frontal cortex-to-white matter ratios of 0.7 6 0.2 and 1.3 6 0.2 for both radiotracers in HCs and AD subjects, respectively. There was an excellent linear correlation between 11 C-PiB and 18 F-AZD4694 neocortical SUVR (slope of 0.95, r 5 0.99, P , 0.0001). Conclusion: 18 F-AZD4694 displays imaging characteristics nearly identical to those of 11 C-PiB. The low white matter and high cortical binding in AD indicate that this tracer is well suited to both clinical and research use.

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Section: Discussionmentioning

confidence: 54%

Head-to-Head Comparison of ¹¹C-PiB and ¹⁸F-AZD4694 (NAV4694) for β-Amyloid Imaging in Aging and Dementia

et al. 2013

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“…Emerging noninvasive imaging strategies include amyloidtargeting probes for PET, such as florbetaben (47), flutemetamol (48), and florbetapir (49) (recently accepted by the Food and Drug Administration) (50). Information from these tracers is now correlated with the well-studied amyloid ligand 11 C-Pittsburgh compound B ( 11 C-PiB) (51,52). However, volumetric MR imaging assessments of hippocampal volumes and measurements of cerebral glucose metabolism using 18 F-FDG PET can also aid the diagnosis of Alzheimer disease.…”

Section: Potential Of Pet/mr Imaging In Cardiologymentioning

confidence: 99%

Preclinical and Translational PET/MR Imaging

et al. 2014

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Combined PET and MR imaging (PET/MR imaging) has progressed tremendously in recent years. The focus of current research has shifted from technologic challenges to the application of this new multimodal imaging technology in the areas of oncology, cardiology, neurology, and infectious diseases. This article reviews studies in preclinical and clinical translation. The common theme of these initial results is the complementary nature of combined PET/MR imaging that often provides additional insights into biologic systems that were not clearly feasible with just one modality alone. However, in vivo findings require ex vivo validation. Combined PET/MR imaging also triggers a multitude of new developments in image analysis that are aimed at merging and using multimodal information that ranges from better tumor characterization to analysis of metabolic brain networks. The combination of connectomics information that maps brain networks derived from multiparametric MR data with metabolic information from PET can even lead to the formation of a new research field that we would call cometomics that would map functional and metabolic brain networks. These new methodologic developments also call for more multidisciplinarity in the field of molecular imaging, in which close interaction and training among clinicians and a variety of scientists is needed. Mol ecular imaging of small animals for biomedical research is an emerging field (1). It penetrates successfully into areas that are historically dominated by ex vivo molecular biology methods and therefore bears an enormous potential. Exploiting the full range of options of noninvasive visualization and quantification of metabolism, disease-specific dysfunction, therapy response, and cell trafficking requires that specific biomarkers yield information about molecular and functional processes as well as morphologic details. Single-modality imaging, such as stand-alone PET, SPECT, MR imaging, CT, or ultrasound, is often unable to provide the desired comprehensive information. Dedicated small-animal PET/CT and SPECT/CT scanners have been well received in the biomedical imaging sciences and have set the stage for a new combined imaging modality, PET/MR imaging, which has been introduced and successfully applied in biomedical studies (2,3). PET and MR imaging are both distinct modalities offering great versatility for advanced imaging applications in various fields of biomedicine. The combination of these two modalities into a single device merges functional and morphologic information from MR imaging with molecular PET data. The strength of PET lies in its high detection sensitivity and accurate quantification, but PET lacks good spatial resolution and tissue contrast. MR imaging, however, enables highresolution imaging of morphology with good soft-tissue contrast, detects endogenous metabolite distributions using spectroscopy, and allows dynamic acquisition of tissue perfusion and additional functional parameters (4).Thus, PET/MR imaging paves the way for noninvasive imaging to...

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“…PET ligands (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15) have made it possible to investigate the fibrillar amyloid-b (Ab) burden in living people; to clarify its relationship to the dementia, mild cognitive impairment (MCI), and preclinical stages of Alzheimer disease (AD); to characterize the extent to which cross-sectional measurements predict subsequent clinical declines; to track longitudinal changes; and to help evaluate Ab-modifying treatments.…”

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Improved Power for Characterizing Longitudinal Amyloid-β PET Changes and Evaluating Amyloid-Modifying Treatments with a Cerebral White Matter Reference Region

et al. 2015

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In this article, we describe an image analysis strategy with improved power for tracking longitudinal amyloid-β (Aβ) PET changes and evaluating Aβ-modifying treatments. Methods: Our aims were to compare the power of template-based cerebellar, pontine, and cerebral white matter reference regions to track 24-mo florbetapir standardized uptake value (SUV) ratio (SUVR) changes; to relate those changes to 24-mo clinical declines; and to evaluate Aβ-modifying treatments in Aβ-positive (Aβ1) and Aβ-negative (Aβ−) patients with probable Alzheimer dementia (pAD), in patients with mild cognitive impairment (MCI), in cognitively normal controls (NCs), and in cognitively normal apolipoprotein E4 (APOE4) carriers and noncarriers. We used baseline and follow-up (∼24 mo) florbetapir PET scans from 332 Aβ1 and Aβ− subjects participating in the multicenter Alzheimer's Disease Neuroimaging Initiative. Each of the proposed analyses included 31 pAD patients, 187 MCI patients, and 114 NCs. Cerebral-to-white matter, cerebellar, and pontine SUVRs were characterized in terms of their longitudinal variability; their power to track longitudinal fibrillar Aβ increases in Aβ1 and Aβ− subgroups and cognitively normal APOE4 carriers and noncarriers; the sample sizes needed to detect attenuated accumulation of or clearance of fibrillar Aβ accumulation in randomized clinical trials; and their ability to relate 24-mo fibrillar Aβ increases to clinical declines. Results: As predicted, cerebral-to-white matter SUVR changes were significantly less variable and had significantly greater power to detect 24-mo fibrillar Aβ increases and evaluate Aβ-modifying treatment effects in Aβ1 pAD, MCI, and NC subjects and cognitively normal APOE4 carriers. They were also distinguished by the ability to detect significant associations between 24-mo Aβ increases and clinical declines. Conclusion: A cerebral white matter reference region may improve the power to track longitudinal fibrillar Aβ increases, to characterize their relationship to longitudinal clinical declines, and to evaluate Aβ-modifying treatments in randomized clinical trials. PET ligands (1-15) have made it possible to investigate the fibrillar amyloid-b (Ab) burden in living people; to clarify its relationship to the dementia, mild cognitive impairment (MCI), and preclinical stages of Alzheimer disease (AD); to characterize the extent to which cross-sectional measurements predict subsequent clinical declines; to track longitudinal changes; and to help evaluate Ab-modifying treatments.Researchers commonly compute a semiquantitative cerebral-toreference region standardized uptake value ratio (SUVR) using PET counts from a cerebral region of interest (ROI) and from a whole cerebellar (2,3), cerebellar gray matter (10), or pontine (8) reference ROI that is thought to be relatively devoid of fibrillar Ab. Less commonly, researchers compute a cerebral-to-reference region distribution volume ratio or other quantitative measures using longer, dynamically acquired PET scans and the same cerebral and refe...

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Comparison of 11C-PiB and 18F-florbetaben for Aβ imaging in ageing and Alzheimer’s disease

Abstract: FBB, while having a narrower dynamic range than PiB, clearly distinguished HC from AD patients, with a comparable effect size. FBB seems a suitable (18)F radiotracer for imaging AD pathology in vivo.

Cited by 166 publications

References 33 publications

Head-to-Head Comparison of ¹¹C-PiB and ¹⁸F-AZD4694 (NAV4694) for β-Amyloid Imaging in Aging and Dementia

Head-to-Head Comparison of ¹¹C-PiB and ¹⁸F-AZD4694 (NAV4694) for β-Amyloid Imaging in Aging and Dementia

Preclinical and Translational PET/MR Imaging

Improved Power for Characterizing Longitudinal Amyloid-β PET Changes and Evaluating Amyloid-Modifying Treatments with a Cerebral White Matter Reference Region

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Comparison of 11C-PiB and 18F-florbetaben for Aβ imaging in ageing and Alzheimer’s disease

Abstract: FBB, while having a narrower dynamic range than PiB, clearly distinguished HC from AD patients, with a comparable effect size. FBB seems a suitable (18)F radiotracer for imaging AD pathology in vivo.

Cited by 166 publications

References 33 publications

Head-to-Head Comparison of 11C-PiB and 18F-AZD4694 (NAV4694) for β-Amyloid Imaging in Aging and Dementia

Head-to-Head Comparison of 11C-PiB and 18F-AZD4694 (NAV4694) for β-Amyloid Imaging in Aging and Dementia

Preclinical and Translational PET/MR Imaging

Improved Power for Characterizing Longitudinal Amyloid-β PET Changes and Evaluating Amyloid-Modifying Treatments with a Cerebral White Matter Reference Region

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Product

Resources

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Head-to-Head Comparison of ¹¹C-PiB and ¹⁸F-AZD4694 (NAV4694) for β-Amyloid Imaging in Aging and Dementia

Head-to-Head Comparison of ¹¹C-PiB and ¹⁸F-AZD4694 (NAV4694) for β-Amyloid Imaging in Aging and Dementia