title: 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.
authors.affiliation: Center for Molecular Imaging Science (CMIS), RIKEN, Japan.
authors.forename: Misato
authors.initials: M
authors.lastname: Takashima-Hirano
authors.forename: Syusaku
authors.initials: S
authors.lastname: Tazawa
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Takahashi
authors.forename: Hisashi
authors.initials: H
authors.lastname: Doi
authors.forename: Masaaki
authors.initials: M
authors.lastname: Suzuki
mesh_terms: D002250:Carbon Radioisotopes / Q000737:chemistry; D006801:Humans; D007192:Indenes / Q000138:chemical synthesis*; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis*; D044094:Receptors, Melatonin / Q000032:analysis*
chemical_list: D002250:Carbon Radioisotopes; D007192:Indenes; D019275:Radiopharmaceuticals; D044094:Receptors, Melatonin; C495910:ramelteon