Synthesis, structure activity relationship, radiolabeling and preclinical evaluation of high affinity ligands for the ion channel of the N-methyl-d-aspartate receptor as potential imaging probes for positron emission tomography.
作者： Pieter J. Klein , Johannes A.M. Christiaans , Athanasios Metaxas , Robert C. Schuit , Adriaan A. Lammertsma
DOI: 10.1016/J.BMC.2014.12.029
关键词:
摘要: Abstract The N-methyl- d -aspartate receptor (NMDAr) is involved in many neurological and psychiatric disorders including Alzheimer’s disease schizophrenia. Currently, it not possible to assess NMDAr availability vivo. purpose of this study was develop a positron emission tomography (PET) ligand for the ion channel. A series di- tri-N-substituted diarylguanidines synthesized. In addition, vitro binding affinity channel rat forebrain membrane fractions assessed. Compounds 10, 11 32 were radiolabeled with either carbon-11 or fluorine-18. Ligands [11C]10 [18F]32 evaluated ex vivo B6C3 mice. Biodistribution studies showed higher uptake regions compared cerebellum. 54% 70% activity brain at 60 min due intact tracer. Pre-treatment MK-801 (0.6 mg·kg−1, ip) slightly decreased NMDAr-specific [18F]32, but [11C]10. As such has best characteristics as PET tracer NMDAr.
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