Formation of 1-[123I]iodobutane in labeling [123I]iomazenil by iododestannylation: implications for the reaction mechanism.

The benzodiazepine receptor tracer [123I]iomazenil (Ro 16-0154, IMZ) can be prepared in close to theoretical specific activity by the reaction of its tributyltin precursor (IMZ-SnBu3) with [123I]NaI in the presence of Iodogen. However, the labeling reaction is associated with variably high amounts of a volatile 123I byproduct. The purpose of these experiments was to characterize the volatile byproduct and to examine the effect on the course of the reaction of the following variables: solvent (MeOH, EtOH, HOAc, H2O), pH (2-7), oxidizing agent (chloramine-T, Iodogen, AcO2H), reaction temperature (22-128 degrees C) and structure of ArSnR3. The order of reactivity of oxidizing agents, at 22 degrees C for 30 min, was chloramine-T > Iodogen > AcO2H. Raising the pH above 5.8 reduced the labeling, whereas raising the temperature increased the yield up to a maximum at 120 degrees (90%); at higher temperatures, decomposition occurred. The best conditions were 50 micrograms precursor, 50 microL 0.02 M chloramine-T; in aqueous HOAc (pH 3.3) at 120 degrees for 30 min. Variable amounts of volatile byproduct were observed for chloramine-T at different temperatures (2-21%) and for the three oxidizing agents at room temperature (3-22%). By contrast, the Bu3Sn derivatives of IBF, epidepride, beta-CIT and the Me3Sn derivative of beta-CIT gave high labeling yields with peracetic acid at room temperature, and < or = 2% volatile radioactivity. The volatile byproduct from the [123I]IMZ preparations was identified as I-[123I]iodobutane by its trapping characteristics and by its retention time in two different HPLC systems. Volatile activity was not generated in the absence of Bu3Sn precursor and was not due to the presence of impurities in the tributylstannyl precursor.