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

Publisher: Springer-Verlag Berlin Country of Publication: Germany NLM ID: 101140988 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1619-7089 (Electronic) Linking ISSN: 16197070 NLM ISO Abbreviation: Eur J Nucl Med Mol Imaging Subsets: MEDLINE

Original Publication: Berlin : Springer-Verlag Berlin, 2002-

Brain*/diagnostic imaging ; Brain*/metabolism ; Membrane Glycoproteins*/metabolism ; Nerve Tissue Proteins*/metabolism; Animals ; Macaca mulatta/metabolism ; Positron-Emission Tomography/methods

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 [ ¹¹ C]UCB-J and [ ¹⁸ F]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.
(© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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S10 OD016261 United States OD NIH HHS; UL1 TR001863 United States TR NCATS NIH HHS; P51 OD011107 United States OD NIH HHS; R21 MH120615 United States MH NIMH NIH HHS; S10 RR025063 United States RR NCRR NIH HHS; R24 HL085794 United States HL NHLBI NIH HHS; S10 RR029245 United States RR NCRR NIH HHS; U42 OD027094 United States OD NIH HHS

Keywords: In utero; Nonhuman primate; Positron emission tomography; SV2A; Synaptogenesis

0 (Membrane Glycoproteins)
0 (Nerve Tissue Proteins)

Date Created: 20220528 Date Completed: 20220825 Latest Revision: 20230323

20231215

PMC9826644

10.1007/s00259-022-05825-6

35633376