TY - JOUR T1 - [11C]-CIMBI5: A novel 5-HT2A agonist PET tracer JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 490 LP - 490 VL - 50 IS - supplement 2 AU - Anders Ettrup AU - Mikael Palner AU - Nic Gillings AU - Kjell Nagren AU - Sune Keller AU - Merence Sibomana AU - Lars Rasmussen AU - Jacob Madsen AU - Mikael Begtrup AU - Gitte Knudsen Y1 - 2009/05/01 UR - http://jnm.snmjournals.org/content/50/supplement_2/490.abstract N2 - 490 Objectives Receptor agonist PET tracers have a better potential than antagonist tracers to reflect displacement under endogenous neurotransmitter release. The aim of the current study was to validate a novel 5-HT2A agonist PET tracer in the pig brain. Methods The high-affinity 5-HT2A selective agonist N-(2-[11C-OCH3]methoxybenzyl)-2,5-dimethoxy-4-iodophenethylamine ([11C]-INBMeO, [11C]-CIMBI5) was radiolabelled by methylation of the N-Boc-protected precursor. In five Danish Landrace pigs, [11C]-CIMBI5 was given as IV bolus injection, and the pigs were subsequently PET scanned with a HRRT camera (n=5). Three of the pigs were scanned a second time, now under treatment with the 5-HT2A antagonist ketanserin (3 mg/kg bolus, 1 mg/kg*hour infusion). Results Compared to cerebellum, [11C]-CIMBI5 showed a high cortical uptake, and from the time activity curves the cortex to cerebellum ratio (AUCcortex/AUCcerebellum) was ~1.4. Following ketanserin pre-treatment, the cortical binding of [11C]-CIMBI5 was reduced to cerebellar levels. Conclusions The novel agonist PET tracer [11C]-CIMBI5 distributes in the pig brain in a pattern compatible with the known 5-HT2A receptor distribution, and its binding is displaceable by ketanserin. Thus, [11C]-CIMBI5 is a promising candidate for human 5-HT2A PET scanning, although the relatively high cerebellum binding, indicative of a high non-specific binding, may compromise the possibility to detect changes in [11C]-CIMBI5 binding following changes in extracellular 5-HT levels. Changes in either the 11C-labeling site or modifications in the chemical structure may improve the signal-to-noise ratio. ER -