A metabolically stable PET tracer for imaging synaptic vesicle protein 2A: synthesis and preclinical characterization of [
Brain imaging
Metabolically stable
Nonhuman primates
PET
SDM-16 [18F]SDM-16
SV2A
Journal
European journal of nuclear medicine and molecular imaging
ISSN: 1619-7089
Titre abrégé: Eur J Nucl Med Mol Imaging
Pays: Germany
ID NLM: 101140988
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
received:
01
07
2021
accepted:
17
10
2021
pubmed:
12
11
2021
medline:
12
4
2022
entrez:
11
11
2021
Statut:
ppublish
Résumé
To quantify the synaptic vesicle glycoprotein 2A (SV2A) changes in the whole central nervous system (CNS) under pathophysiological conditions, a high affinity SV2A PET radiotracer with improved in vivo stability is desirable to minimize the potential confounding effect of radiometabolites. The aim of this study was to develop such a PET tracer based on the molecular scaffold of UCB-A, and evaluate its pharmacokinetics, in vivo stability, specific binding, and nonspecific binding signals in nonhuman primate brains, in comparison with [ The racemic SDM-16 (4-(3,5-difluorophenyl)-1-((2-methyl-1H-imidazol-1-yl)methyl)pyrrolidin-2-one) and its two enantiomers were synthesized and assayed for in vitro binding affinities to human SV2A. We synthesized the enantiopure [ SDM-16 was synthesized in 3 steps with 44% overall yield and has the highest affinity (K We have successfully synthesized a novel SV2A PET tracer [
Identifiants
pubmed: 34761284
doi: 10.1007/s00259-021-05597-5
pii: 10.1007/s00259-021-05597-5
pmc: PMC8940841
doi:
Substances chimiques
Aminoacridines
0
Membrane Glycoproteins
0
Radiopharmaceuticals
0
SDM
50815-81-1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1482-1496Subventions
Organisme : NIA NIH HHS
ID : R01 AG058773
Pays : United States
Organisme : NIA NIH HHS
ID : R01AG058773
Pays : United States
Informations de copyright
© 2021. The Author(s).
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