title: A rapid and efficient method for the radiosynthesis and purification of [125I]SCH23982.
abstract: The radiosynthesis of (1R)-(+)-1-phenyl-3-methyl-7-[125I]iodo-8-hydroxy- 2,3,4,5-tetrahydro-1H-3-benzazepine (commonly referred to as SCH23982) and its use as a high affinity D1 dopamine antagonist ligand have been reported previously. We now provide a simple and inexpensive protocol for the rapid and efficient synthesis of this radioligand based on the Cloramine-T-catalyzed reaction between the commercially available precursor (R)-(+)-1-phenyl-3-methyl- 8-hydroxy-2,3,4,5-tetrahydro-1H-3-benzazepine and carrier-free sodium [125I]iodide. [125I]SCH23982 is separated rapidly (within 20 min) from the precursor and reaction byproducts (e.g., chlorinated precursor, SCH23390) by reverse-phase HPLC on a C-8 column. The major iodinated product has been identified as SCH23982 based on co-chromatography with authentic SCH23982, UV spectral characteristics, and biological activity. The chromatographic effluent containing the active product is adsorbed on a C-18 Sep-Pak cartridge to remove mobile-phase constituents and permit it to be eluted and diluted to the desired concentration; this technique is used also for periodic repurification. Our synthesis protocol results in final purified product that incorporates ca. 50% of the initial 125I (tested using starting quantities of 1-10 mCi Na125I); the final product has a specific activity of ca. 2500 +/- 350 Ci/mmol. Data from in vitro receptor autoradiographic and homogenate studies with this radioligand are consistent with previously reported values in terms of expected receptor distribution, affinity, and density (KD of 1.0 nM, Bmax of 1400 fmol/mg protein in rat striatal membranes).
authors.affiliation: Brain and Development Research Center, University of North Carolina School of Medicine, Chapel Hill 27599.
authors.forename: C P
authors.initials: CP
authors.lastname: Lawler
authors.forename: J H
authors.initials: JH
authors.lastname: Gilmore
authors.forename: D H
authors.initials: DH
authors.lastname: Mooney
authors.forename: M A
authors.initials: MA
authors.lastname: Mayleben
authors.forename: J R
authors.initials: JR
authors.lastname: Atashi
authors.forename: B E
authors.initials: BE
authors.lastname: Mileson
authors.forename: S D
authors.initials: SD
authors.lastname: Wyrick
authors.forename: R B
authors.initials: RB
authors.lastname: Mailman
mesh_terms: D000818:Animals; D001345:Autoradiography; D001552:Benzazepines / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000302:isolation & purification / Q000378:metabolism; D001921:Brain / Q000648:ultrastructure; D001923:Brain Chemistry; D002700:Chloramines; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007457:Iodine Radioisotopes; D007553:Isotope Labeling / Q000379:methods; D008253:Macaca mulatta; D008297:Male; D051381:Rats; D011954:Receptors, Dopamine / Q000032:analysis / Q000378:metabolism; D012974:Sodium Iodide; D013997:Time Factors; D014105:Tosyl Compounds
chemical_list: C049558:8-iodo-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7-ol; D001552:Benzazepines; D002700:Chloramines; D007457:Iodine Radioisotopes; D011954:Receptors, Dopamine; D014105:Tosyl Compounds; C016300:chloramine-T; C046765:1-phenyl-3-methyl-8-hydroxy-2,3,4,5-tetrahydro-1H-3-benzazepine; D012974:Sodium Iodide