Synthesis of 2-iodo- and 2-phenyl-[11C]melatonin: potential PET tracers for melatonin binding sites.
Two 11C-labelled melatonin derivatives, 2-iodo-[11C]melatonin (2-iodo-5-methoxy-N[11C-acetyl]-tryptamine, an agonist) and 2-phenyl-[11C]melatonin (2-phenyl-5-methoxy-N[11C-acetyl]tryptamine, a putative antagonist) were synthesized from [11C]carbon dioxide. The reaction sequence was common to both compounds and consisted of three steps: (i) carbonylation of methyl magnesium bromide with [11C]carbon dioxide, (ii) conversion of the adduct to [11C]acetyl chloride, (iii) acetylation of the amine precursors (2-iodo-5-methoxy-tryptamine or 2-phenyl-5-methoxy-tryptamine) with [11C]acetyl chloride. The precursors were especially prepared. The radiochemical yield was 19% for 2-iodomelatonin and 32% for 2-phenymelatonin, based on [11C]carbon dioxide; the specific activity ranged from 300 to 600 mCi/mumol. Both labelled 2-substituted-melatonins are intended to be used as radiotracers to study melatonin binding sites in man with positron emission tomography.
Chen
J J
JJ
Section of Radiology and Nuclear Medicine, Hamilton Health Sciences Corporation, McMaster University Medical Centre, Ont., Canada.
Fiehn-Schulze
B
B
Brough
P A
PA
Snieckus
V
V
Firnau
G
G
D000107:Acetylation; D001665:Binding Sites; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics*; D006801:Humans; D007202:Indicators and Reagents; D013058:Mass Spectrometry; D008550:Melatonin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism*; D019906:Nuclear Magnetic Resonance, Biomolecular; D011956:Receptors, Cell Surface / Q000032:analysis*; D018160:Receptors, Cytoplasmic and Nuclear / Q000032:analysis*; D044094:Receptors, Melatonin; D014055:Tomography, Emission-Computed
C100536:2-phenylmelatonin; D002250:Carbon Radioisotopes; D007202:Indicators and Reagents; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D044094:Receptors, Melatonin; C044556:2-iodomelatonin; D008550:Melatonin