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Synthesis and in vivo evaluation of [18F]UCB-J for PET imaging of synaptic vesicle glycoprotein 2A (SV2A)

  • Songye LiEmail author
  • Zhengxin CaiEmail author
  • Wenjie Zhang
  • Daniel Holden
  • Shu-fei Lin
  • Sjoerd J. Finnema
  • Anupama Shirali
  • Jim Ropchan
  • Stephane Carre
  • Joel Mercier
  • Richard E. Carson
  • Nabeel Nabulsi
  • Yiyun Huang
Original Article
Part of the following topical collections:
  1. Translational research

Abstract

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 [11C]UCB-J, a PET radiotracer with high affinity and selectivity toward SV2A; however, the short radioactive half-life (20 min for 11C) places some limitations on its broader application. Herein, we report the first synthesis of the longer-lived 18F-labeled counterpart (half-life: 110 min), [18F]UCB-J, and its evaluation in nonhuman primates.

Methods

[18F]UCB-J was synthesized from the iodonium precursors. PET imaging experiments with [18F]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 [11C]UCB-J.

Results

[18F]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 [11C]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 [18F]UCB-J. [18F]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.

Keywords

SV2A PET Radiotracer Fluorination Nonhuman primates Alzheimer’s disease 

Notes

Acknowledgements

The authors thank the staff at the Yale PET Center for their expert assistance in this work. Z.C. was supported by the NIH/NIBIB under award number K01 EB023312.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving animals were in accordance with the ethical standards of the Yale University Institutional Animal Care and Use Committee.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.PET Center, Department of Radiology and Biomedical ImagingYale UniversityNew HavenUSA
  2. 2.Department of Nuclear MedicineWest China Hospital of Sichuan UniversityChengduChina
  3. 3.UCB BiopharmaBraine-l’AlleudBelgium

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