Preclinical Evaluation of Benzazepine-Based PET Radioligands (R)- and (S)-¹¹C-Me-NB1 Reveals Distinct Enantiomeric Binding Patterns and a Tightrope Walk Between GluN2B- and σ₁-Receptor-Targeted PET Imaging.

ABSTRACT: The study aims to investigate the performance characteristics of the enantiomers of ¹¹C-Me-NB1, a recently reported PET imaging probe that targets the GluN2B subunit of N-methyl-d-aspartate (NMDA) receptors. Methods: Reference compound Me-NB1 (inhibition constant for hGluN1/GluN2B, 5.4 nM) and the phenolic precursor were prepared via multistep synthesis. Following chiral resolution by high-performance liquid chromatography, enantiopure precursor compounds, (R)-NB1 and (S)-NB1, were labeled with ¹¹C and validated in rodents using in vitro/ex vivo autoradiography, PET experiments, and dose-response studies. To illustrate the translational relevance, (R)-¹¹C-Me-NB1 was validated in autoradiographic studie

SUBMITTER: Haider A 

PROVIDER: S-EPMC6681693 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature