A new radioactive tracer, [11C]Cimbi-36, was tested in 29 healthy volunteers for brain imaging using PET scans. This tracer binds to serotonin 2A receptors, which are involved in mood and perception, and is an agonist, meaning it activates the receptor rather than blocking it. High uptake in the brain matched known locations of these receptors. A two-tissue compartment model using arterial blood samples gave the most accurate measurements. In five subjects given a blocker drug (ketanserin), tracer binding decreased in cortical areas but not in the cerebellum, confirming the tracer's specificity and that the cerebellum can serve as a reference region. This is the first agonist PET radioligand to successfully image these receptors in humans.
A radiolabeled agonist tracer, (11)C-CIMBI-5, was developed for PET imaging of the serotonin 2A (5-HT2A) receptor in the brain. In vitro assays showed CIMBI-5 is a high-affinity agonist at the 5-HT2A receptor. Ex vivo rat studies demonstrated a specific binding ratio of 0.77 ± 0.07 in the frontal cortex, which was reduced to cerebellar levels after ketanserin treatment, indicating selective binding. PET studies in pigs revealed a cortical binding potential of 0.46 ± 0.12 and a target-to-background ratio similar to the antagonist tracer (18)F-altanserin. Ketanserin treatment reduced cortical binding to cerebellar levels, confirming selective in vivo binding. (11)C-CIMBI-5 is a promising tool for investigating 5-HT2A agonist binding in the living human brain.