RT Journal Article SR Electronic T1 Effect of fenfluramine on 5-HT1B binding of [11C]AZ10419369 in the primate brain JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 489 OP 489 VO 50 IS supplement 2 A1 Sjoerd Finnema A1 Andrea Varrone A1 Tzung-Jeng Hwang A1 Balazs Gulyas A1 Edward Pierson A1 Lars Farde A1 Christer Halldin YR 2009 UL http://jnm.snmjournals.org/content/50/supplement_2/489.abstract AB 489 Objectives We recently reported an initial PET-study using the selective serotonin 5-HT1B receptor radioligand [11C]AZ10419369. The 5-HT1B receptor has a role in the modulation of synaptic serotonin release. The aim of this study was to assess the sensitivity of [11C]AZ10419369 binding to pharmacological manipulation of endogenous serotonin levels in monkey. Methods A total of 12 PET measurements were conducted using i.v. bolus injection of [11C]AZ10419369 in four cynomolgus monkeys. On each of six experimental days a baseline measurement was followed by a displacement measurement in which fenfluramine (1.0 or 5.0 mg/kg) was infused i.v. between 15 and 20 min after radioligand injection. Emission data were acquired for 123 min using the HRRT PET-system. The specific binding ratio was calculated as the ratio of the area under the curve (45-123 min) of target to reference region (cerebellum). The displacement effect was estimated as relative change (%) in specific binding ratio. Results Administration of fenfluramine had no evident effect on radioactivity in cerebellum. After administration of fenfluramine (1.0 and 5.0 mg/kg), the respective binding ratios decreased in occipital cortex by 33 ± 11% and 49 ± 19%, in striatopallidal complex by 18 ± 23% and 38 ± 9% and in midbrain by 28 ± 18% and 49 ± 16%, respectively. Conclusions This preliminary study supports that the new 5-HT1B-ligand [11C]AZ10419369 is sensitive to endogenous serotonin levels in vivo. The radioligand may accordingly serve as a tool to further examine serotonin-related brain functions and psychiatric disorders, as well as effects of drugs on endogenous levels of serotonin in brain.