Synthesis of two new 11C-labelled a7 nicotinic acetylcholine receptor ligands.

Introduction
NS-9011 (4-[5-(4-Methoxy-phenyl)-[1,3,4]oxadiazol-2-yl]-1,4-diaza-bizyclo[3.2.2]nonane) and NS-9030 (4-[5-(3-Methoxy-phenyl)-[1,3,4]oxadiazol-2-yl]-1,4-diaza-the desmethyl precursor compounds with [11C]methyltriflate. The precursor compounds showed a high reactivity towards [11C]iodomethane, unfortunately not in the desired labelling position. In order to decrease the selectivity for the undesired compound(s) [11C]methyltriflate instead of [11C]iodomethane was used. The higher reactivity of the [11C]methyltriflate in combination with elevated temperature of 60 °C and using water as solvent should result in a considerable decrease in selectivity.
Methods
The radiosynthesis was carried out in a modified TracerLab C system (GEMS) equipped with a reaction loop instead of the glass reactor in the heating zone of the module. [11C]iodomethane was subsequently passed over silver triflate at 200 °C and through the reaction loop containing the precursor solution (prepared from 0.5 – 1.0 mg precursor and 30μl of 0.5 M NaOH solution) and 30 μl of water) heated to 60 °C. The reaction mixture was transferred with eluent into a HPLC valve and injected on a ReproSil-Pur 120 C18-Aq 5μ (125 mm x 10 mm) HPLC column. An eluent composed of 10 % Ethanol (NS-9011) or 13 % Ethanol (NS-9030) and buffer solution (40 ml sodium phosphate (Braun) per 1000 ml adjusted to pH 2 with phosphorc acid was used for purification.The product peak was collected, diluted and concentrated on a Phenomenex Strata X cartridge. The radiotracer was eluted with acetone (1.5 ml). Evaporation was performed manually in a heating block (70 °C) in a stream of nitrogen. The product was dissolved in 500 μl of physiological NaCl solution. Radiochemical purity was determined on a radio-HPLC system on a ReproSil-Pur 120 C18-Aq 5μ (250 mm x 4.6 mm) HPLC column.
Results and Discussion
By applying the reaction conditions described above, despite highly favoured competing labelling sites in the precursor molecule up to 0.5 GBq of tracer compound could be synthesized. The product was obtained in high radiochemical purity (>95 %). Comparison of the UV trace of authentic standard compound and the radioactivity signal of radiotracer spiked with standard compound showed a full match of radioactivity and UV signal. The yield was sufficient for first animal experiments and the reaction conditions were not further optimized.