A rapid and efficient method for the radiosynthesis and purification of [¹²⁵I]SCH23982

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 Na¹²⁵1); 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 (K_d of 1.0 nM. B_max of 1400 fmol/mg protein in rat striatal membranes).