RT Journal Article
T1 Synthesis and Biological Evaluation of Quinoxaline Derivatives for  PET Imaging of the NMDA Receptor
A1 Roscales García, Silvia
A1 Selena Milicevic Sephton, 
A1 Peter T. Vetterli, 
A1 Valentina Pedani, 
A1 Stjepko Cermak, 
A1 Aristeidis  Chiotellis, 
A1 Adrienne Muller Herde, 
A1 Roger Schibli, 
A1 Yves P. Auberson, 
A1 Simon M. Ametamey, 
AB Due to the biological complexity of the N-methyl-D-aspartate receptor (NMDAR), the development of a positron emission tomography radiotracer for the imaging of NMDAR has met with limited success. Recent studies have established the presence of GluN2A subunit of the NMDAR in the heart and its role in the regulation of intracellular calcium levels. In our efforts to develop an imaging agent for the GluN2A subunit, we designed three new compounds based on a quinoxaline scaffold. The synthesis of the analogues was based on a two-step Kabachnik-Fields reaction in sequence with Suzuki cross-coupling and acid hydrolysis. They exhibited comparable high binding affinity values below 5 nM. A two-step radiolabeling procedure was successfully developed for the synthesis of [18F]1. [18F]1 was obtained in a modest overall radiochemical yield of 5.5 4.2%, a good specific radioactivity of 254 158 GBq/lmol, and a radiochemical purity > 99%. While compounds 2 and 3 showed comparable binding affinity towards NMDAR, sluggish radiolabeling, prevented their further evaluation. For [18F]1, in vitro autoradiography on rat heart slices demonstrated heterogeneous but unspecific accumulation, whereas for the brain a high in vitro specificity towards NMDAR, could be demonstrated.
PB Wiley-VHCA AG, Zurich, Switzerland
YR 2017
FD 2017
LK https://hdl.handle.net/20.500.14352/125740
UL https://hdl.handle.net/20.500.14352/125740
LA eng
NO Milicevic Sephton S, Vetterli PT, Pedani V, et al. Synthesis and Biological Evaluation of Quinoxaline Derivatives for PET Imaging of the NMDA Receptor. Helvetica Chimica Acta 2017;100:e1700204. https://doi.org/10.1002/hlca.201700204.
DS Docta Complutense
RD 27 feb 2026