ABSTRACT
Carbon-11-labeled aminoalkylindole derivatives (1-butyl-7-[(11)C]methoxy-1H-indol-3-yl)(naphthalene-1-yl)methanone ([(11)C]3), 1-butyl-7-[(11)C]methoxy-3-(naphthalene-1-ylmethyl)-1H-indole ([(11)C]5), and 1-butyl-7-[(11)C]methoxy-3-(naphthalene-2-yl)-1H-indole ([(11)C]8) were prepared by O-[(11)C]methylation of their corresponding precursors with [(11)C]CH3OTf under basic condition (2N NaOH) and isolated by a simplified solid-phase extraction (SPE) method in 50-60% radiochemical yields based on [(11)C]CO2 and decay corrected to end of bombardment (EOB). The overall synthesis time from EOB was 23 min, the radiochemical purity was >99%, and the specific activity at end of synthesis (EOS) was 185-555 GBq/µmol.
Subject(s)
Alcoholism/diagnosis , Indoles/chemistry , Radiopharmaceuticals/chemistry , Receptors, Cannabinoid/chemistry , Alcoholism/diagnostic imaging , Carbon Radioisotopes/chemistry , Humans , Indoles/chemical synthesis , Isotope Labeling , Ligands , Positron-Emission Tomography , Radiography , Radiopharmaceuticals/chemical synthesis , Receptors, Cannabinoid/metabolism , Solid Phase ExtractionABSTRACT
The reference standards 4a-b, 6a-b, 7a-c, and desmethylated precursors 9a-b, 10a-b, 8a-c were synthesized from 4-methoxyaniline, ethyl 2-chloro-acetoacetate and substituted benzene-1,2-diamines with 3, 5, 6 steps in 61-67%, 34-41%, 23-31%, and with 4, 6, 7 steps in 49-57%, 28-35%, 20-27% overall chemical yield, respectively. The target tracers [(11)C]4a-b, [(11)C]6a-b, [(11)C]7a-c were synthesized from their corresponding precursors with [(11)C]CH3OTf through O-[(11)C]methylation and isolated by simplified SPE in 40-60% decay corrected radiochemical yields at EOB, with 185-370 GBq/µmol specific activity at EOS.