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.