Synthesis and in vivo characterization of D-(+)-(N1-[11C]methyl)-2-Br-LSD: a radioligand for positron emission tomographic studies of serotonin 5-HT2 receptors.
D-(+)-N1-Methyl-2-Br-LSD (MBL), which displays high affinity and selectivity for serotonin receptors in vitro, has been labeled with carbon-11 for localization of cerebral serotonin 5-HT2 receptors by positron emission tomography. [11C]MBL was prepared from [11C]iodomethane and D-(+)-2-Br-LSD within 20 min from end of bombardment. The average specific activity of [11C]MBL was 2300 mCi/mumol and the average radiochemical yield was 17%, both at end of synthesis. The in vivo regional distribution of radioactivity in brain after i.v. administration of [11C]MBL to mice paralleled the known density of serotonin 5-HT2 receptors. The maximum specific binding, defined by a frontal cortex to cerebellum radioactivity concentration ratio of 5.4 to 1, was reached 30 min postinjection. Administration of ketanserin, a potent serotonin 5-HT2 receptor antagonist, markedly blocked radioligand binding in all brain regions examined except cerebellum.
Lever
J R
JR
Department of Environmental Health Sciences, Johns Hopkins Medical Institutions, Baltimore, MD 21205.
Dannals
R F
RF
Wilson
A A
AA
Ravert
H T
HT
Scheffel
U
U
Hoffman
B J
BJ
Hartig
P R
PR
Wong
D F
DF
Wagner
H N
HN
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging*; D002250:Carbon Radioisotopes; D007553:Isotope Labeling / Q000379:methods*; D008238:Lysergic Acid Diethylamide / Q000031:analogs & derivatives*; D008297:Male; D051379:Mice; D011985:Receptors, Serotonin / Q000378:metabolism*; D014055:Tomography, Emission-Computed
D002250:Carbon Radioisotopes; D011985:Receptors, Serotonin; C058328:N(1)-methyl-2-bromo-lysergic acid diethylamide; D008238:Lysergic Acid Diethylamide