First-in-Human Study of18F-SynVesT-2: An SV2A PET Imaging Probe with Fast Brain Kinetics and High Specific Binding
Open accessAbstract
PET imaging of synaptic vesicle glycoprotein 2A allows for noninvasive quantification of synapses. This first-in-human study aimed to evaluate the kinetics, test–retest reproducibility, and extent of specific binding of a recently developed synaptic vesicle glycoprotein 2A PET ligand, (R)-4-(3-(18F-fluoro)phenyl)-1-((3-methylpyridin-4-yl)methyl)pyrrolidine-2-one (18F-SynVesT-2), with fast brain kinetics. Methods: Nine healthy volunteers participated in this study and were scanned on a High Resolution Research Tomograph scanner with 18F-SynVesT-2. Five volunteers were scanned twice on 2 different days. Five volunteers were rescanned with preinjected levetiracetam (20 mg/kg, intravenously). Arterial blood was collected to calculate the plasma free fraction and generate the arterial input function. Individual MR images were coregistered to a brain atlas to define regions of interest for generating time–activity curves, which were fitted with 1- and 2-tissue-compartment (1TC and 2TC) models to derive the regional distribution volume (VT). The regional nondisplaceable binding potential (BPND) was calculated from 1TC VT, using the centrum semiovale (CS) as the reference region. Results:18F-SynVesT-2 was synthesized with high molar activity (187 ± 69 MBq/nmol, n = 19). The parent fraction of 18F-SynVesT-2 in plasma was 28% ± 8% at 30 min after injection, and the plasma free fraction was high (0.29 ± 0.04). 18F-SynVesT-2 entered the brain quickly, with an SUVpeak of 8 within 10 min after injection. Regional time–activity curves fitted well with both the 1TC and the 2TC models; however, VT was estimated more reliably using the 1TC model. The 1TC VT ranged from 1.9 ± 0.2 mL/cm3 in CS to 7.6 ± 0.8 mL/cm3 in the putamen, with low absolute test–retest variability (6.0% ± 3.6%). Regional BPND ranged from 1.76 ± 0.21 in the hippocampus to 3.06 ± 0.29 in the putamen. A 20-min scan was sufficient to provide reliable VT and BPND. Conclusion:18F-SynVesT-2 has fast kinetics, high specific uptake, and low nonspecific uptake in the brain. Consistent with the nonhuman primate results, the kinetics of 18F-SynVesT-2 is faster than the kinetics of 11C-UCB-J and 18F-SynVesT-1 in the human brain and enables a shorter dynamic scan to derive physiologic information on cerebral blood flow and synapse density.
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Recent human scans with [18F]SynVesT-2 demonstrate slightly lower binding potential but faster kinetics than [18F]SynVesT-1.
“Recent human scans with [ 18 F] SynVesT-2 demonstrate slightly lower binding potential but faster kinetics than [ 18 F]SynVesT-1”
From Challenges and rewards of in vivo synaptic density imaging, and its application to the study of depression (2025) · cites this paper as [126]
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- Authors
- Drake, L. R., Wu, Y., Naganawa, M., Asch, R., Zheng, C., Najafzadeh, S., Pracitto, R., Lindemann, M., Li, S., Ropchan, J., Labaree, D., Emery, P. R., Dias, M., Henry, S., Nabulsi, N., Matuskey, D., Hillmer, A. T., Gallezot, J.-D., Carson, R. E., Cai, Z., & Huang, Y.
- Affiliations
- Yale University (US)
- ORCID
- Venue
- Journal of Nuclear Medicine
- Publisher
- Society of Nuclear Medicine
- Published
- 2024-02-15
- Volume
- 65
- Issue
- 3
- Pages
- 462-469
- ISSN
- 0161-5505 (ISSN-L)
- 2159-662X
- PMC
- PMC10924160
- OpenAlex
- W4391845259
- Cited by
- 18
- References
- 35
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 2 · 2022: 1 · 2021: 3
- FWCI
- 3.55
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Nuclear Medicine (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (KL2TR001862)
- National Institute of Neurological Disorders and Stroke (R01NS123183)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Radiopharmaceutical Chemistry and Applications
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- SV2A, PET imaging probe, synapse quantification, volume of distribution, binding potential, test-retest reproducibility, first-in-human study, radioligand synthesis, putamen
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