Towards NR2B receptor selective imaging agents for PET-synthesis and evaluation of N-[11C]-(2-methoxy)benzyl (E)-styrene-, 2-naphthyl- and 4-trifluoromethoxyphenylamidine.
Three potent and selective 11C-labelled NR2B antagonists have been synthesized and evaluated as PET ligands. The brain uptake of the compounds in mice varied substantially and was dominated by metabolism. One compound was found to have favourable uptake and retention in the brain, as well as a binding pattern consistent with the expression of the target receptor as measured by in vitro autoradiography. However, the metabolism of the compounds tested was too rapid to allow for in vivo imaging.
Arstad
Erik
E
Hammersmith Imanet Ltd, Cyclotron Building, Du Cane Road, London W12 ONN, UK. erik.arstad@csc.mrc.ac.uk
Platzer
Stefan
S
Berthele
Achim
A
Pilowsky
Lyn S
LS
Luthra
Sajinder K
SK
Wester
Hans-Jürgen
HJ
Henriksen
Gjermund
G
D000578:Amidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000840:Anisoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002247:Carbon Isotopes; D008024:Ligands; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D049268:Positron-Emission Tomography / Q000379:methods*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
D000578:Amidines; D000840:Anisoles; D002247:Carbon Isotopes; D008024:Ligands; C514595:N-(2-methoxy)benzyl 4-trifluomethoxyphenylamidine; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate