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-(+)-Nl-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/μ mol 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.