RT Journal Article
SR Electronic
T1 [11C]-CIMBI5: A novel 5-HT2A agonist PET tracer
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 490
OP 490
VO 50
IS supplement 2
A1 Anders Ettrup
A1 Mikael Palner
A1 Nic Gillings
A1 Kjell Nagren
A1 Sune Keller
A1 Merence Sibomana
A1 Lars Rasmussen
A1 Jacob Madsen
A1 Mikael Begtrup
A1 Gitte Knudsen
YR 2009
UL http://jnm.snmjournals.org/content/50/supplement_2/490.abstract
AB 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.