The preparation of a carbon-11 labelled neurohormone--[11C]melatonin

Melatonin, a hormone of the pineal gland, has been labelled with the positron-emitting radionuclide, carbon-11 (t1/2 = 20.4 min), for study in vivo by positron emission tomography. Thus a novel labelling agent, [11C]acetyl chloride, was prepared by the carbonation of methylmagnesium bromide with cyclotron-produced [11C]carbon dioxide followed by treatment with phthaloyl dichloride. Acylation of 5-methoxytryptamine then affords [11C]melatonin, which is purified by HPLC and formulated for intravenous injection. The preparation requires 35 min from the end of radionuclide production. It provides [11C]melatonin in 13% radiochemical yield (decay-corrected from 11CO2) and in high specific activity. Radiochemical and chemical purity were demonstrated by HPLC and TLC. The validity of the radiosynthesis was also confirmed by a parallel synthesis of [13C]melatonin and examination of the product by 13C-NMR spectroscopy and mass spectrometry.