Dataset Information

In vivo measurement of widespread synaptic loss in Alzheimer's disease with SV2A PET.

ABSTRACT:

Introduction

Synaptic loss is a robust and consistent pathology in Alzheimer's disease (AD) and the major structural correlate of cognitive impairment. Positron emission tomography (PET) imaging of synaptic vesicle glycoprotein 2A (SV2A) has emerged as a promising biomarker of synaptic density.

Methods

We measured SV2A binding in 34 participants with early AD and 19 cognitively normal (CN) participants using [¹¹ C]UCB-J PET and a cerebellar reference region for calculation of the distribution volume ratio.

Results

We observed widespread reductions of SV2A binding in medial temporal and neocortical brain regions in early AD compared to CN participants. These reductions were largely maintained after correction for volume loss and were more extensive than decreases in gray matter volume.

Conclusion

We were able to measure widespread synaptic loss due to AD using [¹¹ C]UCB-J PET. Future studies will continue to evaluate the utility of SV2A PET for tracking AD progression and for monitoring potential therapies.

SUBMITTER: Mecca AP

PROVIDER: S-EPMC7383876 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Publications

In vivo measurement of widespread synaptic loss in Alzheimer's disease with SV2A PET.

Mecca Adam P AP Chen Ming-Kai MK O'Dell Ryan S RS Naganawa Mika M Toyonaga Takuya T Godek Tyler A TA Harris Joanna E JE Bartlett Hugh H HH Zhao Wenzhen W Nabulsi Nabeel B NB Wyk Brent C Vander BCV Varma Pradeep P Arnsten Amy F T AFT Huang Yiyun Y Carson Richard E RE van Dyck Christopher H CH

Alzheimer's & dementia : the journal of the Alzheimer's Association 20200513 7

<h4>Introduction</h4>Synaptic loss is a robust and consistent pathology in Alzheimer's disease (AD) and the major structural correlate of cognitive impairment. Positron emission tomography (PET) imaging of synaptic vesicle glycoprotein 2A (SV2A) has emerged as a promising biomarker of synaptic density.<h4>Methods</h4>We measured SV2A binding in 34 participants with early AD and 19 cognitively normal (CN) participants using [<sup>11</sup> C]UCB-J PET and a cerebellar reference region for calculat ...[more]

PMID: 32400950

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Project description:Quantitative imaging biomarkers are widely used in PET for both research and clinical applications, yet bias in the underlying image data has not been well characterized. In the absence of a readily available reference standard for in vivo quantification, bias in PET images has been inferred using physical phantoms, even though arrangements of this sort provide only a poor approximation of the imaging environment in real patient examinations. In this study, we used data acquired from patient volunteers to assess PET quantitative bias in vivo. Image-derived radioactivity concentrations in the descending aorta were compared with blood samples counted on a calibrated γ-counter. Methods: Ten patients with prostate cancer were studied using 2-(3-(1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl)-ureido)-pentanedioic acid PET/CT. For each patient, 3 whole-body PET/CT image series were acquired after a single administration of the radiotracer: shortly after injection as well as approximately 1 and 4 h later. Venous blood samples were obtained at 8 time points over an 8-h period, and whole blood was counted on a NaI γ-counter. A 10-mm-diameter, 20-mm-long cylindric volume of interest was positioned in the descending thoracic aorta to estimate the PET-derived radioactivity concentration in blood. A triexponential function was fit to the γ-counter blood data and used to estimate the radioactivity concentration at the time of each PET acquisition. Results: The PET-derived and γ-counter-derived radioactivity concentrations were linearly related, with an R 2 of 0.985, over a range of relevant radioactivity concentrations. The mean difference between the PET and γ-counter data was 4.8% ± 8.6%, with the PET measurements tending to be greater. Conclusion: Human image data acquired on a conventional whole-body PET/CT system with a typical clinical protocol differed by an average of around 5% from blood samples counted on a calibrated γ-counter. This bias may be partly attributable to residual uncorrected scatter or attenuation correction error. These data offer an opportunity for the assessment of PET bias in vivo and provide additional support for the use of quantitative imaging biomarkers.

Dataset Information

In vivo measurement of widespread synaptic loss in Alzheimer's disease with SV2A PET.

Introduction

Methods

Results

Conclusion

Publications

In vivo measurement of widespread synaptic loss in Alzheimer's disease with SV2A PET.

Similar Datasets

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