Dataset Information

Head-to-head comparison of tau positron emission tomography tracers [¹⁸F]flortaucipir and [¹⁸F]RO948.

ABSTRACT:

Purpose

[¹⁸F]flortaucipir binds to paired helical filament tau and accurately identifies tau in Alzheimer's disease (AD). However, "off-target" binding interferes with the quantification of [¹⁸F]flortaucipir in several brain regions. Recently, other tau PET tracers have been developed. Here, we compare [¹⁸F]flortaucipir with the novel tau tracer [¹⁸F]RO948 head-to-head in vivo.

Methods

We included 18 participants with AD, three with amyloid-β-positive amnestic mild cognitive impairment, and four healthy controls. All underwent [¹⁸F]flortaucipir (80-100 min) and [¹⁸F]RO948 (70-90) PET scans within approximately 1 month. Four study participants underwent 0-100-min dynamic scanning. Standardized uptake value ratios (SUVRs) were created using an inferior cerebellar reference region.

Results

Neocortical tracer retention was highly comparable using both SUVR and distribution volume ratio-1 values obtained from dynamic scans. However, [¹⁸F]RO948 retention was significantly higher in the entorhinal cortex and lower in the basal ganglia, thalamus, and choroid plexus compared with [¹⁸F]flortaucipir. Increased off-target binding was observed with age for both tracers. Several cases exhibited strong [¹⁸F]RO948 retention in the skull/meninges. This extra-cerebral signal, however, did not affect diagnostic accuracy and remained relatively unchanged when re-examining a subsample after 1 year. Kinetic modeling showed an increase in [¹⁸F]flortaucipir SUVR over the scanning interval, compared with a plateau for [¹⁸F]RO948.

Conclusion

[¹⁸F]RO948 and [¹⁸F]flortaucipir bound comparably in neocortical regions, but [¹⁸F]RO948 showed higher retention in the medial temporal lobe and lower intracerebral "off-target" binding. Time-dependent bias of SUVR estimates may prove less of a factor with [¹⁸F]RO948, compared with previous tau ligands.

SUBMITTER: Smith R

PROVIDER: S-EPMC6974501 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Publications

Head-to-head comparison of tau positron emission tomography tracers [<sup>18</sup>F]flortaucipir and [<sup>18</sup>F]RO948.

Smith Ruben R Schöll Michael M Leuzy Antoine A Jögi Jonas J Ohlsson Tomas T Strandberg Olof O Hansson Oskar O

European journal of nuclear medicine and molecular imaging 20191014 2

<h4>Purpose</h4>[<sup>18</sup>F]flortaucipir binds to paired helical filament tau and accurately identifies tau in Alzheimer's disease (AD). However, "off-target" binding interferes with the quantification of [<sup>18</sup>F]flortaucipir in several brain regions. Recently, other tau PET tracers have been developed. Here, we compare [<sup>18</sup>F]flortaucipir with the novel tau tracer [<sup>18</sup>F]RO948 head-to-head in vivo.<h4>Methods</h4>We included 18 participants with AD, three with amyl ...[more]

PMID: 31612245

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Project description:ImportanceThe diagnostic performance of second-generation tau positron emission tomographic (PET) tracers is not yet known.ObjectiveTo examine the novel tau PET tracer RO948 F 18 ([18F]RO948) performance in discriminating Alzheimer disease (AD) from non-AD neurodegenerative disorders.Design, setting, and participantsIn this diagnostic study, 613 participants in the Swedish BioFINDER-2 study were consecutively enrolled in a prospective cross-sectional study from September 4, 2017, to August 28, 2019. Participants included 257 cognitively unimpaired controls, 154 patients with mild cognitive impairment, 100 patients with AD dementia, and 102 with non-AD neurodegenerative disorders. Evaluation included a comparison of tau PET tracer [18F]RO948 with magnetic resonance imaging (MRI) and cerebrospinal fluid and a head-to-head comparison between [18F]RO948 and flortaucipir F 18 ([18F]flortaucipir) in patients with semantic variant primary progressive aphasia (svPPA).Exposures[18F]RO948 (all patients) and [18F]flortaucipir (3 patients with svPPA) tau PET; MRI (hippocampal volume, composite temporal lobe cortical thickness, whole-brain cortical thickness) and cerebrospinal fluid measures (p-tau181 and amyloid Aβ42 and Aβ40 ratio[Aβ42/Aβ40], and Aβ42/p-tau181 ratio).Main outcomes and measuresStandard uptake value ratios (SUVRs) in 4 predefined regions of interest (ROIs) reflecting Braak staging scheme for tau pathology and encompass I-II (entorhinal cortex), III-IV (inferior/middle temporal, fusiform gyrus, parahippocampal cortex, and amygdala), I-IV, and V-VI (widespread neocortical areas), area under the receiver operating characteristic curve (AUC) values, and subtraction images between [18F]RO948 and [18F]flortaucipir.ResultsDiagnostic groups among the 613 participants included cognitively unimpaired (mean [SD] age, 65.8 [12.1] years; 117 men [46%]), mild cognitive impairment (age, 70.8 [8.3] years; 82 men [53%]), AD dementia (age, 73.5 [6.7] years; 57 men [57%]), and non-AD disorders (age, 70.5 [8.6] years; 41 men [40%]). Retention of [18F]RO948 was higher in AD dementia compared with all other diagnostic groups. [18F]RO948 could distinguish patients with AD dementia from individuals without cognitive impairment and those with non-AD disorders, and the highest AUC was obtained using the I-IV ROI (AUC = 0.98; 95% CI, 0.96-0.99 for AD vs no cognitive impairment and AUC = 0.97; 95% CI, 0.95-0.99 for AD vs non-AD disorders), which outperformed MRI (highest AUC = 0.91 for AD vs no cognitive impairment using whole-brain thickness, and AUC = 0.80 for AD vs non-AD disorders using temporal lobe thickness) and cerebrospinal fluid measures (highest AUC = 0.94 for AD vs no cognitive impairment using Aβ42/p-tau181, and AUC = 0.93 for AD vs non-AD disorders using Aβ42/Aβ40). Generally, tau PET positivity using [18F]RO948 was observed only in Aβ-positive cases or in MAPT R406W mutation carriers. Retention of [18F]RO948 was not pronounced in patients with svPPA, and head-to-head comparison revealed lower temporal lobe uptake than with [18F]flortaucipir.Conclusions and relevanceIn this study, elevated [18F]RO948 SUVRs were most often seen among Aβ-positive cases, which suggests that [18F]RO948 has high specificity for AD-type tau and highlights its potential as a diagnostic marker in the differential diagnosis of AD.

Project description:BackgroundThe progression of Alzheimer's dementia (AD) can be classified into three stages: cognitive unimpairment (CU), mild cognitive impairment (MCI), and AD. The purpose of this study was to implement a machine learning (ML) framework for AD stage classification using the standard uptake value ratio (SUVR) extracted from 18F-flortaucipir positron emission tomography (PET) images. We demonstrate the utility of tau SUVR for AD stage classification. We used clinical variables (age, sex, education, mini-mental state examination scores) and SUVR extracted from PET images scanned at baseline. Four types of ML frameworks, such as logistic regression, support vector machine (SVM), extreme gradient boosting, and multilayer perceptron (MLP), were used and explained by Shapley Additive Explanations (SHAP) to classify the AD stage.ResultsOf a total of 199 participants, 74, 69, and 56 patients were in the CU, MCI, and AD groups, respectively; their mean age was 71.5 years, and 106 (53.3%) were men. In the classification between CU and AD, the effect of clinical and tau SUVR was high in all classification tasks and all models had a mean area under the receiver operating characteristic curve (AUC) > 0.96. In the classification between MCI and AD, the independent effect of tau SUVR in SVM had an AUC of 0.88 (p < 0.05), which was the highest compared to other models. In the classification between MCI and CU, the AUC of each classification model was higher with tau SUVR variables than with clinical variables independently, which yielded an AUC of 0.75(p < 0.05) in MLP, which was the highest. As an explanation by SHAP for the classification between MCI and CU, and AD and CU, the amygdala and entorhinal cortex greatly affected the classification results. In the classification between MCI and AD, the para-hippocampal and temporal cortex affected model performance. Especially entorhinal cortex and amygdala showed a higher effect on model performance than all clinical variables in the classification between MCI and CU.ConclusionsThe independent effect of tau deposition indicates that it is an effective biomarker in classifying CU and MCI into clinical stages using MLP. It is also very effective in classifying AD stages using SVM with clinical information that can be easily obtained at clinical screening.

Project description:Purpose18F-APN-1607 is a novel tau positron emission tomography (PET) tracer characterized with high binding affinity for 3- and 4-repeat tau deposits. The aim was to analyze the spatial distribution of 18F-APN-1607 PET imaging in Alzheimer's disease (AD) subjects with different stages and to investigate the relationship between the change of tau deposition and overall disease progression.MethodsWe retrospectively analyzed the 18F-APN-1607 PET imaging of 31 subjects with clinically and imaging defined as AD. According to the Mini-Mental State Examination (MMSE) score, patients were divided into three groups, namely, mild (≥21, n = 7), moderate (10-20, n = 16), and severe (≤9, n = 8). PET imaging was segmented to 70 regions of interest (ROIs) and extracted the standard uptake value (SUV) of each ROI. SUV ratio (SUVR) was calculated from the ratio of SUV in different brain regions to the cerebellar cortex. The regions were defined as positive and negative with unsupervised cluster analysis according to SUVR. The SUVRs of each region were compared among groups with the one-way ANOVA or Kruskal-Wallis H test. Furthermore, the correlations between MMSE score and regional SUVR were calculated with Pearson or Spearman correlation analysis.ResultsThere were no significant differences among groups in gender (χ2 = 3.814, P = 0.161), age of onset (P = 0.170), age (P = 0.109), and education level (P = 0.065). With the disease progression, the 18F-APN-1607 PET imaging showed the spread of tau deposition from the hippocampus, posterior cingulate gyrus (PCG), and lateral temporal cortex (LTC) to the parietal and occipital lobes, and finally to the frontal lobe. Between the mild and moderate groups, the main brain areas with significant differences in 18F-APN-1607 uptake were supplementary motor area (SMA), cuneus, precuneus, occipital lobule, paracentral lobule, right angular gyrus, and parietal, which could be used for early disease progression assessment (P < 0.05). There were significant differences in the frontal lobe, right temporal lobe, and fusiform gyrus between the moderate and severe groups, which might be suitable for the late-stage disease progression assessment (P < 0.05).Conclusion18F-APN-1607 PET may serve as an effective imaging marker for visualizing the change pattern of tau protein deposition in AD patients, and its uptake level in certain brain regions is closely related to the severity of cognitive impairment. These indicate the potential of 18F-APN-1607 PET for the in vivo evaluation of the progression of AD.

Dataset Information

Head-to-head comparison of tau positron emission tomography tracers [¹⁸F]flortaucipir and [¹⁸F]RO948.

Purpose

Methods

Results

Conclusion

Publications

Head-to-head comparison of tau positron emission tomography tracers [<sup>18</sup>F]flortaucipir and [<sup>18</sup>F]RO948.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Head-to-head comparison of tau positron emission tomography tracers [18F]flortaucipir and [18F]RO948.

Purpose

Methods

Results

Conclusion

Publications

Head-to-head comparison of tau positron emission tomography tracers [<sup>18</sup>F]flortaucipir and [<sup>18</sup>F]RO948.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Head-to-head comparison of tau positron emission tomography tracers [¹⁸F]flortaucipir and [¹⁸F]RO948.