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

P.J. Klein; J.A.M. Christiaans; A. Metaxas; R.C. Schuit; A.A. Lammertsma; B.N.M. van Berckel; A.D. Windhorst

doi:https://doi.org/10.1016/j.bmc.2014.12.029

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

P.J. Klein, J.A.M. Christiaans, A. Metaxas, R.C. Schuit, A.A. Lammertsma, B.N.M. van Berckel, A.D. Windhorst

Radiology and Nuclear Medicine (VUmc)

Research output: Contribution to journal › Article › Academic › peer-review

16 Citations (Scopus)

Abstract

The N-methyl-d-aspartate receptor (NMDAr) is involved in many neurological and psychiatric disorders including Alzheimer's disease and schizophrenia. Currently, it is not possible to assess NMDAr availability in vivo. The purpose of this study was to develop a positron emission tomography (PET) ligand for the NMDAr ion channel. A series of di- and tri-N-substituted diarylguanidines was synthesized. In addition, in vitro binding affinity for the NMDAr ion channel in rat forebrain membrane fractions was assessed. Compounds 10, 11 and 32 were radiolabeled with either carbon-11 or fluorine-18. Ligands [

Original language	English
Pages (from-to)	1189-1206
Journal	Bioorganic and Medicinal Chemistry
Volume	23
Issue number	5
DOIs	https://doi.org/10.1016/j.bmc.2014.12.029
Publication status	Published - 2015

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https://doi.org/10.1016/j.bmc.2014.12.029

Cite this

Klein, P. J., Christiaans, J. A. M., Metaxas, A., Schuit, R. C., Lammertsma, A. A., van Berckel, B. N. M., & Windhorst, A. D. (2015). 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. Bioorganic and Medicinal Chemistry, 23(5), 1189-1206. https://doi.org/10.1016/j.bmc.2014.12.029

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abstract = "The N-methyl-d-aspartate receptor (NMDAr) is involved in many neurological and psychiatric disorders including Alzheimer's disease and schizophrenia. Currently, it is not possible to assess NMDAr availability in vivo. The purpose of this study was to develop a positron emission tomography (PET) ligand for the NMDAr ion channel. A series of di- and tri-N-substituted diarylguanidines was synthesized. In addition, in vitro binding affinity for the NMDAr ion channel in rat forebrain membrane fractions was assessed. Compounds 10, 11 and 32 were radiolabeled with either carbon-11 or fluorine-18. Ligands [",

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Klein, PJ, Christiaans, JAM, Metaxas, A, Schuit, RC , Lammertsma, AA , van Berckel, BNM & Windhorst, AD 2015, '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', Bioorganic and Medicinal Chemistry, vol. 23, no. 5, pp. 1189-1206. https://doi.org/10.1016/j.bmc.2014.12.029

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. / Klein, P.J.; Christiaans, J.A.M.; Metaxas, A. et al.
In: Bioorganic and Medicinal Chemistry, Vol. 23, No. 5, 2015, p. 1189-1206.

Research output: Contribution to journal › Article › Academic › peer-review

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Klein PJ, Christiaans JAM, Metaxas A, Schuit RC , Lammertsma AA , van Berckel BNM et al. 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. Bioorganic and Medicinal Chemistry. 2015;23(5):1189-1206. doi: https://doi.org/10.1016/j.bmc.2014.12.029