Imaging the fetal nonhuman primate brain with SV2A positron emission tomography (PET)

Samantha Rossano, Takuya Toyonaga, Eric Berg, Isabella Lorence, Krista Fowles, Nabeel Nabulsi, Jim Ropchan, Songye Li, Yunpeng Ye, Zachary Felchner, David Kukis, Yiyun Huang, Helene Benveniste, Alice F. Tarantal, Stephanie Groman, Richard E. Carson

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: Exploring synaptic density changes during brain growth is crucial to understanding brain development. Previous studies in nonhuman primates report a rapid increase in synapse number between the late gestational period and the early neonatal period, such that synaptic density approaches adult levels by birth. Prenatal synaptic development may have an enduring impact on postnatal brain development, but precisely how synaptic density changes in utero are unknown because current methods to quantify synaptic density are invasive and require post-mortem brain tissue. Methods: We used synaptic vesicle glycoprotein 2A (SV2A) positron emission tomography (PET) radioligands [11C]UCB-J and [18F]Syn-VesT-1 to conduct the first assessment of synaptic density in the developing fetal brain in gravid rhesus monkeys. Eight pregnant monkeys were scanned twice during the third trimester at two imaging sites. Fetal post-mortem samples were collected near term in a subset of subjects to quantify SV2A density by Western blot. Results: Image-derived fetal brain SV2A measures increased during the third trimester. SV2A concentrations were greater in subcortical regions than in cortical regions at both gestational ages. Near term, SV2A density was higher in primary motor and visual areas than respective associative regions. Post-mortem quantification of SV2A density was significantly correlated with regional SV2A PET measures. Conclusion: While further study is needed to determine the exact relationship of SV2A and synaptic density, the imaging paradigm developed in the current study allows for the effective in vivo study of SV2A development in the fetal brain.

Original languageEnglish (US)
Pages (from-to)3679-3691
Number of pages13
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Volume49
Issue number11
DOIs
StatePublished - Sep 2022

Bibliographical note

Funding Information:
These studies were supported by National Institutes of Health (NIH) grants (no. MH120615 [SG], and no. U42-OD027094 [AT]), and the California National Primate Research Center base operating grant (no. OD011107). In vivo imaging was performed with instrumentation funded by the NIH (S10 grants RR029245, OD016261, and RR025063), and supported through the Primate Center Multimodal Imaging Core.

Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Keywords

  • In utero
  • Nonhuman primate
  • Positron emission tomography
  • SV2A
  • Synaptogenesis

PubMed: MeSH publication types

  • Journal Article

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