Hussein Bdair, Gabriella Gobbi, Chawki Benkelfat and Alexey Kostikov
McGill University, Canada
Scientific Tracks Abstracts: J Neurol Neurophysiol
Melatonin is a neurohormone, dubbed the hormone of darkness, mainly synthesized by the pineal gland during the dark period of the light-dark cycle and it is known to modulate a wide variety of physiological functions in mammals, such as circadian rhythms, mood, reproduction, immune and cerebrovascular functions. Melatonin-mediated responses occur through the activation of at least two high-affinity G protein-coupled receptors, known as melatonin receptors type 1 and 2 (MT1 and MT2). We herewith report the radiosynthesis of [11C]UCM765, a first-in-kind carbon-11 radiolabelled PET tracer that targets MT2 receptors. The precursor was synthesized by demethylating the recently discovered MT2 partial agonist UCM765 (pKi = 10.18) using boron tribromide (BBr3). The desmethyl precursor was then radiolabelled with C-11 by reacting with [11C] CH3I for 5 min at 90°C followed by HPLC purification. PET studies with [11C]UCM765 in rats revealed a rapid uptake of the tracer in the brain, with subsequent rapid washout from the brain. Extracerebral tracer uptake was also observed in Harderian glands and retinas that express high levels of MT2 receptors. In addition, cerebral and extracerebral [11C]UCM765 uptake was challenged with prior administration of a selective MT2 receptor antagonist 4P-PDOT as a competitor. Our findings warrant further investigations in animal models with subsequent development towards clinical studies in humans.
Hussein Bdair is a PhD student at McGill University, Canada working under the supervision of Dr. Chawki Benkelfat and Dr. Alexey Kostikov. He received his pharmacy degree from University of Kerbala, Iraq in 2013 and his master’s degree in Radiopharmacy from King’s College London, the UK in 2016. He current research investigates the impact of chronic cannabis consumption on serotonin release and, hence, the association between cannabis use and mood lowering through its effect on serotonin release. His expertise is in PET tracer development and radiosynthesis, as well as preclinical PET imaging in rodents.
E-mail: [email protected]