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Assessment of test-retest reproducibility of [18F]SynVesT-1, a novel radiotracer for PET imaging of synaptic vesicle glycoprotein 2A

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

Synaptic abnormalities are associated with many brain disorders. Recently, we developed a novel synaptic vesicle glycoprotein 2A (SV2A) radiotracer [18F]SynVesT-1 and demonstrated its excellent imaging and binding properties in nonhuman primates. The aim of this study was to perform dosimetry calculations in nonhuman primates and to evaluate this tracer in humans and assess its test-retest reliability in comparison with [11C]UCB-J.

Methods

Three rhesus monkeys underwent whole body dynamic PET scanning to estimate the absorbed dose. PET scans in six healthy human subjects were acquired. Time-activity curves (TACs) were generated with defined regions of interest (ROI). Reproducibility of distribution volume (VT) values and its sensitivity to scan duration were assessed with the one-tissue compartment (1TC) model. Non-displaceable binding potential (BPND) was calculated using centrum semiovale as the reference region.

Results

The dosimetry study showed high uptake in the urinary bladder and brain. In humans, [18F]SynVesT-1 displayed high uptake with maximum SUV of ~10 and appropriate kinetics with a quick rise in tracer uptake followed by a gradual clearance. Mean 1TC VT values (mL/cm3) ranged from 3.4 (centrum semiovale) to 19.6 (putamen) and were similar to those of [11C]UCB-J. Regional BPND values were 2.7–4.7 in gray matter areas, and mean BPND values across all ROIs were ~ 21% higher than those of [11C]UCB-J. The absolute test-retest variability of VT and BPND was excellent (< 9%) across all brain regions.

Conclusions

[18F]SynVesT-1 demonstrates outstanding characteristics in humans: fast and high brain uptake, appropriate tissue kinetics, high levels of specific binding, and excellent test-retest reproducibility of binding parameters. As such, [18F]SynVesT-1 is proved to be a favorable radiotracer for SV2A imaging and quantification in humans.

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Acknowledgments

The authors appreciate the excellent technical assistance of the staff at the Yale University PET Center. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NIH.

Funding

This study was funded by the Michael J. Fox Foundation and National Institutes of Health (US) R01AG052560 & R01AG065474. This publication was also made possible by CTSA Grant UL1 RR024139 jointly from the National Center for Research Resources (NCRR) and the National Center for Advancing Translational Sciences (NCATS), components of the National Institutes of Health (NIH).

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Author notes

  1. Songye Li and Mika Naganawa are co-first authors.

    Richard E. Carson and Yiyun Huang are co-senior authors.

Authors and Affiliations

  1. PET Center, Yale University School of Medicine, PO Box 208048, New Haven, CT, 06520-8048, USA

    Songye Li, Mika Naganawa, Richard Pracitto, Soheila Najafzadeh, Daniel Holden, Shannan Henry, David Matuskey, Paul R. Emery, Zhengxin Cai, Jim Ropchan, Nabeel Nabulsi, Richard E. Carson & Yiyun Huang

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  1. Songye Li
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Contributions

Yiyun Huang and Richard E. Carson collectively contributed to the conception of the study and its design. Shanna Henry and David Matuskey were responsible for subject recruitment, evaluation, and care. Songye Li, Richard Pracitto, Soheila Najafzadeh, Paul R. Emory, Zhengxin Cai, Jim Ropchan, and Nabeel Nabulsi were responsible for tracer synthesis and quality control tests. Daniel Holden performed data analysis for the dosimetry study. Mika Naganawa performed analysis of imaging data in humans. Songye Li and Mika Naganawa drafted the manuscript. All authors participated in the editing of the manuscript and approved the manuscript and this submission.

Corresponding authors

Correspondence to Songye Li or Yiyun Huang.

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Conflict of interest

The radioligand [18F]SynVesT-1 (formerly referred to as [18F]SDM-8) is contained in the international patent application PCT/US2018/018388, Radiolabeled Pharmaceuticals and Methods of Making and Using Same, filed on February 15, 2018 (Inventors: YH, ZC, SL, NN, and REC). The other authors declare that they have no conflict of interest.

Ethical approval

PET imaging experiments were performed in rhesus monkeys (Macaca mulatta) according to a protocol approved by the Yale University Institutional Animal Care and Use Committee. All applicable international, national, and institutional guidelines for the care and use of animals were followed.

The study protocol involving human participants was approved by the Yale Human Investigation Committee, the Yale-New Haven Hospital Radiation Safety Committee, and the Yale University Radiation Safety Committee. Study procedures were performed in accordance with federal guidelines and regulations of the United States for the protection of human research subjects contained in Title 45 Part 46 of the Code of Federal Regulations (45 CFR 46).

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Informed consent was obtained from all individual participants included in the study.

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Li, S., Naganawa, M., Pracitto, R. et al. Assessment of test-retest reproducibility of [18F]SynVesT-1, a novel radiotracer for PET imaging of synaptic vesicle glycoprotein 2A. Eur J Nucl Med Mol Imaging 48, 1327–1338 (2021). https://doi.org/10.1007/s00259-020-05149-3

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