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[ 18 F]-Florbetazine ([ 18 F]-92) is a selective PET tracer for β-amyloid (Aβ) depositions with a novel diaryl-azine scaffold to reduce lipophilicity and to achieve higher gray-to-white matter contrast. We aimed to assess its diagnostic value in Alzheimer's disease (AD) and pharmacokinetics characteristics in human subjects., Methods: Six healthy controls (HCs) and nine AD patients underwent dynamic PET examination with [ 18 F]-Florbetazine and a structural MRI scan. The time-activity-curves (TACs) for volumes of interest (VOIs) in cerebral cortex, cerebellar cortex and cerebral white matter was depicted and their standardized uptake value ratios (SUVRs) with cerebellar cortex as reference were compared between HCs and AD patients. The cerebral gray-to-white matter SUV ratio (GWR) was also calculated., Results: In HCs, radioactivities in the cerebral cortex VOIs were homogeneously low and at the same level as in cerebellar cortex, while in AD patients, cortical VOIs expected to contain Aβ exhibited high radioactivity. Cerebral cortex SUVRs remain relatively low in HCs while keep increasing along with time in AD patients. After 15 min, the cerebral cortex SUVRs became significant higher in AD patients compared to HCs with 100 % discrimination accuracy. In AD patients, GWR remained over 1.3 for all time intervals and visual inspection showed lower uptake in cerebral white matter compared to cerebral cortex., Conclusion: [ 18 F]-Florbetazine PET showed high uptake on Aβ plaques and high gray-to-white contrast in AD patients that are favorable in visual read. [ 18 F]-Florbetazine can be potentially used for detection and quantification of Aβ depositions in the living human brain., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

One of the earliest indicators of Alzheimer's disease pathology is the presence of beta-amyloid (Αβ) protein deposition. Significant amyloid deposition is evident even in older adults who exhibit little or no overt cognitive or memory impairment. Hippocampal-based processes that help distinguish between highly similar memory representations may be the most susceptible to early disease pathology. Amyloid associations with memory have been difficult to establish, possibly because typical memory assessments do not tax hippocampal operations sufficiently. Thus, the present study utilized a spatial mnemonic discrimination task designed to tax hippocampal pattern separation/completion processes in a sample of cognitively normal middle-aged and older adults (53-98 years old) who underwent PET 18 F-Florbetapir Αβ scanning. The degree of interference between studied and new information varied, allowing for an examination of mnemonic discrimination as a function of mnemonic similarity. Results indicated that greater beta-amyloid burden was associated with poorer discrimination across decreasing levels of interference, suggesting that even subtle elevation of beta-amyloid in cognitively normal adults is associated with impoverished performance on a hippocampally demanding memory task. The present study demonstrates that degree of amyloid burden negatively impacts the ability of aging adults to accurately distinguish old from increasingly distinct new information, providing novel insight into the cognitive expression of beta-amyloid neuropathology., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Positron emission tomography (PET)-based staging of regional amyloid deposition has recently emerged as a promising tool for sensitive detection and stratification of pathology progression in Alzheimer's Disease (AD). Here we present an updated methodological framework for PET-based amyloid staging using region-specific amyloid-positivity thresholds and assess its longitudinal validity using serial PET acquisitions. We defined region-specific thresholds of amyloid-positivity based on Florbetapir-PET data of 13 young healthy individuals (age ≤ 45y), applied these thresholds to Florbetapir-PET data of 179 cognitively normal older individuals to estimate a regional amyloid staging model, and tested this model in a larger sample of patients with mild cognitive impairment (N = 403) and AD dementia (N = 85). 2-year follow-up Florbetapir-PET scans from a subset of this sample (N = 436) were used to assess the longitudinal validity of the cross-sectional model based on individual stage transitions and data-driven longitudinal trajectory modeling. Results show a remarkable congruence between cross-sectionally estimated and longitudinally modeled trajectories of amyloid accumulation, beginning in anterior temporal areas, followed by frontal and medial parietal areas, the remaining associative neocortex, and finally primary sensory-motor areas and subcortical regions. Over 98% of individual amyloid deposition profiles and longitudinal stage transitions adhered to this staging scheme of regional pathology progression, which was further supported by corresponding changes in cerebrospinal fluid biomarkers. In conclusion, we provide a methodological refinement and longitudinal validation of PET-based staging of regional amyloid accumulation, which may help improving early detection and in-vivo stratification of pathologic disease progression in AD., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Background: Sporadic cerebral amyloid angiopathy shows progressive amyloid-β deposition in the wall of small arterioles and capillaries of the leptomeninges and cerebral cortex., Objective: To investigate whether amyloid load and distribution, assessed by florbetapir positron emission tomography (PET), differs between patients with probable CAA-related intracerebral hemorrhage (CAA-ICH) and mild cognitive impairment due to Alzheimer's disease (MCI-AD)., Methods: We assessed [18F]florbetapir uptake in 15 patients with probable CAA-ICH and 20 patients with MCI-AD patients. Global and regional florbetapir retention were assessed using standard uptake values ratio (SUVr) in region-based and voxel-wise approaches. Visual reading of florbetapir scans was performed for all participants. Group comparisons were performed using univariate and multivariate analysis., Results: Global florbetapir retention was lower in patients with CAA-ICH than MCI-AD (median SUVr, 1.33 [1.21-1.41] versus 1.44 [1.35-1.66]; p = 0.032). In the region-based analysis, regional florbetapir distribution was similar between the two groups. There was a trend for an increased occipital/global ratio in CAA-ICH patients compared to MCI-AD (p = 0.060). In the voxel-wise approach, two clusters, one in parietal regions and the other in temporal regions, had higher uptake in MCI-AD relative to CAA patients., Conclusions: Patients with CAA-ICH had a lower global florbetapir PET burden than patients with MCI-AD. Relative florbetapir retention in the posterior regions tended to be higher in CAA patients in region-based analysis but was not statistically different between groups. Investigation on differences in amyloid deposits distribution between groups required a fine-grained voxel-wise analysis. In future studies, selective amyloid tracers are needed to differentiate vascular from parenchymal amyloid.

Pharmacokinetic modelling on dynamic positron emission tomography (PET) data is a quantitative technique. However, the long acquisition time is prohibitive for routine clinical use. Instead, the semi-quantitative standardised uptake value ratio (SUVR) from a shorter static acquisition is used, despite its sensitivity to blood flow confounding longitudinal analysis. A method has been proposed to reduce the dynamic acquisition time for quantification by incorporating cerebral blood flow (CBF) information from arterial spin labelling (ASL) magnetic resonance imaging (MRI) into the pharmacokinetic modelling. In this work, we optimise and validate this framework for a study of ageing and preclinical Alzheimer's disease. This methodology adapts the simplified reference tissue model (SRTM) for a reduced acquisition time (RT-SRTM) and is applied to [ 18 F]-florbetapir PET data for amyloid-β quantification. Evaluation shows that the optimised RT-SRTM can achieve amyloid burden estimation from a 30-min PET/MR acquisition which is comparable with the gold standard SRTM applied to 60 min of PET data. Conversely, SUVR showed a significantly higher error and bias, and a statistically significant correlation with tracer delivery due to the influence of blood flow. The optimised RT-SRTM produced amyloid burden estimates which were uncorrelated with tracer delivery indicating its suitability for longitudinal studies.

The observation that amyloid radiotracers developed for Alzheimer's disease bind to cerebral white matter paved the road to nuclear imaging of myelin in multiple sclerosis. The lysolecithin (lysophosphatidylcholine (LPC)) rat model of demyelination proved useful in evaluating and comparing candidate radiotracers to target myelin. Focal demyelination following stereotaxic LPC injection is larger than lesions observed in experimental autoimmune encephalitis models and is followed by spontaneous progressive remyelination. Moreover, the contralateral hemisphere may serve as an internal control in a given animal. However, demyelination can be accompanied by concurrent focal necrosis and/or adjacent ventricle dilation. The influence of these side effects on imaging findings has never been carefully assessed. The present study describes an optimization of the LPC model and highlights the use of MRI for controlling the variability and pitfalls of the model. The prototypical amyloid radiotracer [ 11 C]PIB was used to show that in vivo PET does not provide sufficient sensitivity to reliably track myelin changes and may be sensitive to LPC side effects instead of demyelination as such. Ex vivo autoradiography with a fluorine radiotracer should be preferred, to adequately evaluate and compare radiotracers for the assessment of myelin content.

Increased brain uptake of 18 F-AV45 visualized by PET is a key biomarker for Alzheimer disease (AD). The SUV ratio (SUVR) is widely used for quantification, but is subject to variability based on choice of reference region and changes in cerebral blood flow. Here we validate the SUVR method against the gold standard volume of distribution (V T ) to assess cross-sectional differences in plaque load. Methods: Dynamic 60-min 18 F-AV45 (291 ± 67 MBq) and 1-min 15 O-H 2 O (370 MBq) scans were obtained in 35 age-matched elderly subjects, including 10 probable AD, 15 amnestic mild cognitive impairment (aMCI), and 10 cognitively healthy controls (HCs). 18 F-AV45 V T was determined from 2-tissue-compartment modeling using a metabolite-corrected plasma input function. Static SUVR was calculated at 50-60 min after injection, using either cerebellar gray matter (SUVR CB ) or whole subcortical white matter (SUVR WM ) as the reference. Additionally, whole cerebellum, pons, centrum semiovale, and a composite region were examined as alternative references. Blood flow was quantified by 15 O-H 2 O SUV. Data are presented as mean ± SEM. Results: There was rapid metabolization of 18 F-AV45, with only 35% of unchanged parent remaining at 10 min. Compared with V T , differences in cortical Aβ load between aMCI and AD were overestimated by SUVR WM (+4% ± 2%) and underestimated by SUVR CB (-10% ± 2%). V T correlated better with SUVR WM (Pearson r: from 0.63 for posterior cingulate to 0.89 for precuneus, P < 0.0001) than with SUVR CB (Pearson r: from 0.51 for temporal lobe [ P = 0.002] to 0.82 for precuneus [ P < 0.0001]) in all tested regions. Correlation results for the alternative references were in between those for CB and WM. 15 O-H 2 O data showed that blood flow was decreased in AD compared with aMCI in cortical regions (-5% ± 1%) and in the reference regions (CB, -9% ± 8%; WM, -8% ± 8%). Conclusion: Increased brain uptake of 18 F-AV45 assessed by the simplified static SUVR protocol does not truly reflect Aβ load. However, SUVR WM is better correlated with V T and more closely reflects V T differences between aMCI and AD than SUVR CB ., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)

The advent of tau-targeted positron emission tomography tracers such as flortaucipir (18F-AV-1451, also known as 18F-T807) have made it possible to investigate the sequence of development of tau and amyloid-β in relationship to age, and to the development of cognitive impairment due to Alzheimer's disease. In this study, flortaucipir tau and florbetapir amyloid positron emission tomography were obtained for 217 subjects including 16 young and 58 older cognitively normal subjects, 95 subjects with mild cognitive impairment (Mini-Mental State Examination 24-30) and 48 subjects with clinically-defined possible or probable Alzheimer's disease (Mini-Mental State Examination >10). Images were evaluated visually and quantitatively by regional and voxel-based cortical to cerebellar standard uptake value ratios. For amyloid positron emission tomography positive (Aβ+) subjects, flortaucipir neocortical standard uptake value ratio was significantly higher with more advanced clinical stage (Alzheimer's disease > mild cognitive impairment > older cognitively normal) and was significantly elevated for Aβ+ mild cognitive impairment and Alzheimer's disease subjects relative to the respective Aβ- subjects. In contrast, florbetapir Aβ- older cognitively normal subjects showed an increase in flortaucipir standard uptake value ratios in mesial temporal lobe regions (amygdala, hippocampus/choroid plexus region of interest) compared to younger cognitively normal subjects, but no increased standard uptake value ratios in neocortical regions. Analysis of covariance with planned contrasts showed no differences in regional or composite posterior neocortical flortaucipir standard uptake value ratio as a function of diagnostic group among Aβ- older cognitively normal or clinically diagnosed Alzheimer's disease or mild cognitive impairment subjects. The pattern of flortaucipir distribution among Aβ+ subjects was reminiscent of the cross-sectional distribution of tau reported in post-mortem pathology studies, in that the most commonly affected regions were the inferior and lateral temporal lobes, the same regions where the first signs of increased retention appeared in Aβ+ cognitively normal subjects. However, there was large variability in extent/density of flortaucipir tau binding among Aβ+ subjects. Although high neocortical flortaucipir retention was consistently associated with an Aβ+ florbetapir positron emission tomography scan, not all Aβ+ subjects had elevated flortaucipir standard uptake value ratios. Finally, within the Aβ+ group, increasing levels of flortaucipir tau binding were associated with increased cognitive impairment, as assessed by Mini-Mental State Examination and Alzheimer's Disease Assessment Scale. These results suggest development of tau beyond the mesial temporal lobe is associated with, and may be dependent on, amyloid accumulation. Further, the results are consistent with the hypothesis that cortical tau is associated with cognitive impairment., (© The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Tau pathology is a hallmark of Alzheimer's disease (AD) but also occurs in normal cognitive aging. Using the tau PET agent (18)F-AV-1451, we examined retention patterns in cognitively normal older people in relation to young controls and AD patients. Age and β-amyloid (measured using PiB PET) were differentially associated with tau tracer retention in healthy aging. Older age was related to increased tracer retention in regions of the medial temporal lobe, which predicted worse episodic memory performance. PET detection of tau in other isocortical regions required the presence of cortical β-amyloid and was associated with decline in global cognition. Furthermore, patterns of tracer retention corresponded well with Braak staging of neurofibrillary tau pathology. The present study defined patterns of tau tracer retention in normal aging in relation to age, cognition, and β-amyloid deposition., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: Magnet resonance image (MRI)-based segmentations are widely used for clinical brain research, especially in conjunction with positron-emission-tomography (PET). Although artifacts due to segmentation errors arise commonly, the impact of these artifacts on PET quantitation has not yet been investigated systematically. Therefore, the aim of this study was to assess the effect of segmentation errors on [(18)F]-AV45 and [(18)F]-FDG PET quantitation, with and without correction for partial volume effects (PVE)., Material and Methods: 119 subjects with both [(18)F]-AV45, and [(18)F]-FDG PET as well as T1-weighted MRI at baseline and at two-year follow-up were selected from the ADNI cohort, and their MRI brain images were segmented using PMOD 3.5. MRIs with segmentation artifacts were masked with the corresponding [(18)F]-FDG PET standard-uptake-value (SUV) images to elucidate and quantify the impact of artifacts on PET analyses for six defined volumes-of-interest (VOI). Artifact volumes were calculated for each VOI, together with error-[%] and root-mean-square-errors (RMSE) in uncorrected and PVE corrected SUV results for the two PET tracers. We also assessed the bias in longitudinal PET data., Results: Artifacts occurred most frequently in the parietal cortex VOI. For [(18)F]-AV45 and [(18)F]-FDG PET, the percentage-errors were dependent on artifact volumes. PVEC SUVs were consequently more distorted than were their uncorrected counterparts. In static and longitudinal assessment, a small subgroup of subjects with large artifacts (≥1500 voxels; ≙5.06 cm³) accounted for much of the PET quantitation bias., Conclusion: Large segmentation artifacts need to be detected and resolved as they considerably bias PET quantitation, especially when PVEC is applied to PET data.

Unlabelled: Classification of subjects on the basis of amyloid PET scans is increasingly being used in research studies and clinical practice. Although qualitative, visual assessment is currently the gold standard approach, automated classification techniques are inherently more reproducible and efficient. The objective of this work was to develop a statistical approach for the automated classification of subjects with different levels of cognitive impairment into a group with low amyloid levels (AβL) and a group with high amyloid levels (AβH) through the use of amyloid PET data from the Alzheimer Disease Neuroimaging Initiative study., Methods: In our framework, an iterative, voxelwise, regularized discriminant analysis is combined with a receiver operating characteristic approach that optimizes the selection of a region of interest (ROI) and a cutoff value for the automated classification of subjects into the AβL and AβH groups. The robustness, spatial stability, and generalization of the resulting target ROIs were evaluated by use of the standardized uptake value ratio for (18)F-florbetapir PET images from subjects who served as healthy controls, subjects who had mild cognitive impairment, and subjects who had Alzheimer disease and were participating in the Alzheimer Disease Neuroimaging Initiative study., Results: We determined that several iterations of the discriminant analysis improved the classification of subjects into the AβL and AβH groups. We found that an ROI consisting of the posterior cingulate cortex/precuneus and the medial frontal cortex yielded optimal group separation and showed good stability across different reference regions and cognitive cohorts. A key step in this process was the automated determination of the cutoff value for group separation, which was dependent on the reference region used for the standardized uptake value ratio calculation and which was shown to have a relatively narrow range across subject groups., Conclusion: We developed a data-driven approach for the determination of an optimal target ROI and an associated cutoff value for the separation of subjects into the AβL and AβH groups. Future work should include the application of this process to other datasets to facilitate the determination of the translatability of the optimal ROI obtained in this study to other populations. Ideally, the accuracy of our target ROI and cutoff value could be further validated with PET-autopsy data from large-scale studies. It is anticipated that this approach will be extremely useful for the enrichment of study populations in clinical trials involving putative disease-modifying therapeutic agents for Alzheimer disease., (© 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Technical factors play a critical role in the production of best-quality amyloid PET images for interpretation. This article provides specific instructions and general technical information about PET brain scanning of β-amyloid neuritic plaques. The focus of tracer-specific information will be on (18)F-florbetapir (indications, contraindications, dosing, administration, uptake time, scanning time, acquisition, processing, biodistribution, radiation dose, adverse events, and display). General scanning information relevant to all amyloid-imaging agents will be also be presented (e.g., mechanism of uptake, safe handling, positioning, prevention of patient motion, processing, and artifacts)., (© 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Recent trends in neurodegeneration research have been aimed at developing new amyloid ligands for the neuroimaging of dementia. Among the positron emission tomography (PET) radiotracers, fluorodeoxyglucose F 18 ((18)F-FDG) is the compound most widely used in the diagnosis of neurodegenerative dementias. However, this compound shows a level of specificity and sensitivity for early Alzheimer's disease detection that is lower than that provided by high-affinity ligands for β-amyloid (Aβ). Among the new widely available fluorine 18 ((18)F)-labeled Aβ ligands, florbetapir F 18 ((18))F-AV-45; Amyvid™) showed clear qualitative and quantitative correlations between in vivo PET imaging and postmortem histopathologic analysis of Aβ. Florbetapir F 18 stands out for its high Aβ affinity and its pharmacokinetic properties that allow 10-minute PET scan imaging within 90 minutes after administration (dose = 370 MBq). Importantly, no safety concerns for florbetapir F 18 were found in preclinical studies. In 2012, the U.S. Food and Drug Administration (FDA) approved Amyvid as a radiotracer helpful for excluding the presence of Aβ in the brain. It was then approved earlier this year by the European Medicines Agency (EMA)., (Copyright 2013 Prous Science, S.A.U. or its licensors. All rights reserved.)

Florbetapir F-18 is a molecular imaging agent combining high affinity for β-amyloid, pharmacokinetic properties that allow positron emission tomography (PET) imaging within a convenient time after dose administration, and the wide availability of the radionuclide fluorine-18. Florbetapir F-18 is prepared by nucleophilic radiofluorination in approximately 60 minutes with a decay-corrected yield of 20%-40% and with a specific activity typically exceeding 100 Ci/mmol. The florbetapir F-18 dissociation constant (K(d)) for binding to β-amyloid in brain tissue from Alzheimer's disease (AD) patients was 3.7 ± 0.3 nmol/L, and the maximum binding capacity (B(max)) was 8800 ± 1600 fmol/mg protein. Autoradiography studies have shown that florbetapir F-18 selectively binds to β-amyloid aggregates in AD patient brain tissue, and the binding intensity is correlated with the density of β-amyloid quantified by standard neuropathologic techniques. Studies in animals revealed no safety concerns and rapid and transient normal brain uptake (6.8% injected dose/g at 2 minutes and 1.9% injected dose/g at 60 minutes in the mouse). Florbetapir F-18 has been well-tolerated in studies of more than 2000 human subjects. Biodistribution studies in humans revealed predominantly hepatobiliary excretion. The whole body effective dose was 7 mSv from a dose of 370 MBq. The pharmacokinetic of florbetapir F-18 make it possible to obtain a PET image with a brief (10 minutes) acquisition time within a convenient time window of 30-90 minutes after dose administration. Clinical studies have demonstrated a clear correlation between in vivo PET imaging with florbetapir F-18 and postmortem histopathologic quantitation of β-amyloid in the brain., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Unlabelled: An (18)F-labeled PET amyloid-beta (Abeta) imaging agent could facilitate the clinical evaluation of late-life cognitive impairment by providing an objective measure for Alzheimer disease (AD) pathology. Here we present the results of a clinical trial with (E)-4-(2-(6-(2-(2-(2-(18)F-fluoroethoxy)ethoxy)ethoxy)pyridin-3-yl)vinyl)-N-methyl benzenamine ((18)F-AV-45 or florbetapir [corrected] F 18)., Methods: An open-label, multicenter brain imaging, metabolism, and safety study of (18)F-AV-45 was performed on 16 patients with AD (Mini-Mental State Examination score, 19.3 +/- 3.1; mean age +/- SD, 75.8 +/- 9.2 y) and 16 cognitively healthy controls (HCs) (Mini-Mental State Examination score, 29.8 +/- 0.45; mean age +/- SD, 72.5 +/- 11.6 y). Dynamic PET was performed over a period of approximately 90 min after injection of the tracer (370 MBq [10 mCi]). Standardized uptake values and cortical-to-cerebellum standardized uptake value ratios (SUVRs) were calculated. A simplified reference tissue method was used to generate distribution volume ratio (DVR) parametric maps for a subset of subjects., Results: Valid PET data were available for 11 AD patients and 15 HCs. (18)F-AV-45 accumulated in cortical regions expected to be high in Abeta deposition (e.g., precuneus and frontal and temporal cortices) in AD patients; minimal accumulation of the tracer was seen in cortical regions of HCs. The cortical-to-cerebellar SUVRs in AD patients showed continual substantial increases through 30 min after administration, reaching a plateau within 50 min. The 10-min period from 50 to 60 min after administration was taken as a representative sample for further analysis. The cortical average SUVR for this period was 1.67 +/- 0.175 for patients with AD versus 1.25 +/- 0.177 for HCs. Spatially normalized DVRs generated from PET dynamic scans were highly correlated with SUVR (r = 0.58-0.88, P < 0.005) and were significantly greater for AD patients than for HCs in cortical regions but not in subcortical white matter or cerebellar regions. No clinically significant changes in vital signs, electrocardiogram, or laboratory values were observed., Conclusion: (18)F-AV-45 was well tolerated, and PET showed significant discrimination between AD patients and HCs, using either a parametric reference region method (DVR) or a simplified SUVR calculated from 10 min of scanning 50-60 min after (18)F-AV-45 administration.

Purpose: The compound (E)-4-(2-(6-(2-(2-(2-(18)F-fluoroethoxy)ethoxy)ethoxy) pyridin-3-yl)vinyl)-N-methylbenzenamine ([(18)F]AV-45) is a novel radiopharmaceutical capable of selectively binding to beta-amyloid (A beta) plaques. This pilot study reports the safety, biodistribution, and radiation dosimetry of [(18)F]AV-45 in human subjects., Methods: In vitro autoradiography and fluorescent staining of postmortem brain tissue from patients with Alzheimer's disease (AD) and cognitively healthy subjects were performed to assess the specificity of the tracer. Biodistribution was assessed in three healthy elderly subjects (mean age: 60.0+/-5.2 years) who underwent 3-h whole-body positron emission tomography (PET)/computed tomographic (CT) scans after a bolus injection of 381.9+/-13.9 MBq of [(18)F]AV-45. Another six subjects (three AD patients and three healthy controls, mean age: 67.7+/-13.6 years) underwent brain PET studies. Source organs were delineated on PET/CT. All subjects underwent magnetic resonance imaging (MRI) for obtaining structural information., Results: In vitro autoradiography revealed exquisitely high specific binding of [(18)F]AV-45 to postmortem AD brain sections, but not to the control sections. There were no serious adverse events throughout the study period. The peak uptake of the tracer in the brain was 5.12+/-0.41% of the injected dose. The highest absorbed organ dose was to the gallbladder wall (184.7+/-78.6 microGy/MBq, 4.8 h voiding interval). The effective dose equivalent and effective dose values for [(18)F]AV-45 were 33.8+/-3.4 microSv/MBq and 19.3+/-1.3 microSv/MBq, respectively., Conclusion: [(18)F]AV-45 binds specifically to A beta in vitro, and is a safe PET tracer for studying A beta distribution in human brain. The dosimetry is suitable for clinical and research application., ((c) 2010 Elsevier Inc. All rights reserved.)