Efficient synthesis of [11C]ramelteon as a positron emission tomography probe for imaging melatonin receptors involved in circadian rhythms

Abstract

Ramelteon (TAK-375) is a novel melatonin receptor agonist that is used for clinical treatment of insomnia. The present report describes radiolabeling of ramelteon with the short-lived positron-emitter 11C (T 1/2=20.4 min) by 2 methods. One method was [11C] methylation of an acetoamide precursor and the other was [11C] acylation of the corresponding amine precursor. First, [11C] methylation method showed the low reproducibility together with the production of many kinds of side products from which the [11C-methyl]Ramelteon was separated with chemical purity of <28% and radiochemical purity of >98%. Whereas, the [11C]acylation method showed high efficiency and reproducibility with a good radiochemical yield (22-43%, decay corrected), high chemical and radiochemical purities (>99% each), and high specific activity (43-162 GBq/μmol) (n=5) after HPLC purification. [ 11C]Ramelteon is a potential positron emission tomography (PET) probe for imaging the melatonin receptor. © 2011 Pharmaceutical Society of Japan.