Synthesis and in vivo evaluation of [18F]UCB-J for PET imaging of synaptic vesicle glycoprotein 2A (SV2A)
Open accessAbstract
Purpose Synaptic abnormalities have been implicated in a variety of neuropsychiatric disorders, including epilepsy, Alzheimer's disease, and schizophrenia. Hence, PET imaging of the synaptic vesicle glycoprotein 2A (SV2A) may be a valuable in vivo biomarker for neurologic and psychiatric diseases. We previously developed [11 C]UCB-J, a PET radiotracer with high affinity and selectivity toward SV2A; however, the short radioactive half-life (20 min for 11 C) places some limitations on its broader application. Herein, we report the first synthesis of the longer-lived 18 F-labeled counterpart (half-life: 110 min), [18 F]UCB-J, and its evaluation in nonhuman primates.Methods [18 F]UCB-J was synthesized from the iodonium precursors. PET imaging experiments with [18 F]UCB-J were conducted in rhesus monkeys to assess the pharmacokinetic and in vivo binding properties. Arterial samples were taken for analysis of radioactive metabolites and generation of input functions. Regional time-activity curves were analyzed using the one-tissue compartment model to derive regional distribution volumes and binding potentials for comparison with [11 C]UCB-J.Results [18 F]UCB-J was prepared in high radiochemical and enantiomeric purity, but low radiochemical yield. Evaluation in nonhuman primates indicated that the radiotracer displayed pharmacokinetic and imaging characteristics similar to those of [11 C]UCB-J, with moderate metabolism rate, high brain uptake, fast and reversible binding kinetics, and high specific binding signals.Conclusion We have accomplished the first synthesis of the novel SV2A radiotracer [18 F]UCB-J. [18 F]UCB-J is demonstrated to be an excellent imaging agent and may prove to be useful for imaging and quantification of SV2A expression, and synaptic density, in humans.
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PET targeting SV2A has matured into a practical readout of synaptic density in vivo, with 11C and 18F ligands enabling cross-species translation.
“PET targeting SV2A has matured into a practical readout of synaptic density in vivo, with carbon-11 (11C) and fluorine-18 (18F) ligands enabling cross-species translation [206,207,208].”
From Synaptic Plasticity—Intrinsic Excitability and Antidepressant Discovery (2026) · cites this paper as [208]
The Introduction describes [11C]UCB-J as a validated synaptic-density imaging biomarker with strong signals in nonhuman primates and humans. The Conclusions report effective [18F]UCB-J imaging in rhesus monkeys, but the Discussion says its low-yield synthesis makes clinical translation challenging. Thus, the paper supports SV2A PET as an in vivo readout and cross-species use of the 11C ligand, but not established cross-species translation of the 18F ligand. (LLM, conf=0.88)
Experimental — accuracy not yet measuredNew imaging tools have the potential to identify biomarkers of psychoplastogen efficacy.
“new imaging tools have the potential to identify biomarkers of psychoplastogen efficacy”
From Psychedelics and Other Psychoplastogens for Treating Mental Illness. (2021) · cites this paper as [105]
The Introduction says SV2A PET imaging may help evaluate drug candidates targeting synaptic repair, and the Conclusions anticipate its use in monitoring treatment efficacy. Neither section addresses psychoplastogens specifically or establishes a biomarker of their efficacy. Page numbers are unavailable in our copy. (LLM, conf=0.84)
Experimental — accuracy not yet measured[11C]UCB-J established high brain uptake and specificity, creating the benchmark for human and preclinical studies.
“[11C]UCB-J established high brain uptake and specificity, creating the benchmark for human and preclinical studies, while [18F]SynVesT-1 and [18F]SynVesT-2 extend accessibility through longer half-life, favorable kinetics, and validated simplified quantification protocols suited to clinical workflows [174,208,209].”
From Synaptic Plasticity—Intrinsic Excitability and Antidepressant Discovery (2026) · cites this paper as [208]
[18F]SynVesT-1 and [18F]SynVesT-2 extend accessibility through longer half-life, favorable kinetics, and validated simplified quantification protocols suited to clinical workflows.
“[11C]UCB-J established high brain uptake and specificity, creating the benchmark for human and preclinical studies, while [18F]SynVesT-1 and [18F]SynVesT-2 extend accessibility through longer half-life, favorable kinetics, and validated simplified quantification protocols suited to clinical workflows [174,208,209].”
From Synaptic Plasticity—Intrinsic Excitability and Antidepressant Discovery (2026) · cites this paper as [208]
The Introduction and Conclusions discuss the longer half-life and imaging properties of [18F]UCB-J, while the Discussion describes [18F]SDM-8. Our copy does not identify either compound as [18F]SynVesT-1 or [18F]SynVesT-2, or address validated simplified quantification protocols for those tracers (searched: SynVesT-1, SynVesT-2, simplified quantification). (LLM, conf=0.76)
Experimental — accuracy not yet measured
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- Authors
- Li, S., Cai, Z., Zhang, W., Holden, D., Lin, S.-F., Finnema, S. J., Shirali, A., Ropchan, J., Carre, S., Mercier, J., Carson, R. E., Nabulsi, N., & Huang, Y.
- Affiliations
- Yale University (US)
- West China Hospital of Sichuan University (CN)
- UCB Pharma (Belgium) (BE)
- Corresponding author
- Li, Songye
- Cai, Zhengxin
- ORCID
- Venue
- European Journal of Nuclear Medicine and Molecular Imaging
- Published
- 2019-06-07
- Volume
- 46
- Issue
- 9
- Pages
- 1952-1965
- ISSN
- 1619-7070 (ISSN-L)
- 1619-7089
- PMC
- PMC6810698
- OpenAlex
- W2948776174
- Cited by
- 59
- References
- 48
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 9 · 2023: 8 · 2022: 10 · 2021: 10 · 2020: 9 · 2018: 2
- FWCI
- 4.79
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- European Journal of Nuclear Medicine and Molecular Imaging (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Yale University
- National Institutes of Health (UL1TR001863)
- National Institute of Biomedical Imaging and Bioengineering (K01EB023312)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Radiopharmaceutical Chemistry and Applications
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- [11C]UCB-J, SV2A, PET radiotracer synthesis, fluorine-18 radiolabeling, rhesus monkeys, pharmacokinetics, binding potential, volume of distribution, epilepsy, Alzheimer's disease, schizophrenia
- MeSH terms
- Animals, Female, Fluorine Radioisotopes, Macaca mulatta, Male, Membrane Glycoproteins, Pyridines, Pyrrolidinones, Radiochemistry, Positron-Emission Tomography, Chemistry Techniques, Synthetic
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