Microwave synthesis of [18F]FPEB in a semi-automated synthesis module

141 Objectives To improve the synthesis of [18F]FPEB (3-[18FF]fluoro-5-(2-pyridinylethynyl)benzonitrile) by application of microwave acceleration in a modified semi-automated fluorination module. Methods A GE TRACERlab® FX-FN module was used with a microwave accelerator with detached resonance cavity. Aqueous [18F]fluoride (70-110 GBq) was collected on a QMA cartridge and eluted with Kryptofix-222 K2CO3 in CH3CN/H2O into a modified Pyrex® V-vial grafted onto a glass collar to allow it to mate with the module’s vessel head. The solution was dried with He(g) flow at 85-105°C followed by 1 mL CH3CN treatment and drying. The vessel was moved to the microwave cavity, precursor 3-nitro-5-(2-pyridinylethynyl)benzonitrile (3-5 mg) in 0.6 ± 0.1 mL DMSO was added, and the mixture was irradiated with a sequence of 3 x 30 sec at 80 watts and maximum temperature 120°C. Control reactions were carried out by thermal heating in the module for 15 min at 120°C. HPLC mobile phase was added and injected on an HPLC with semi-prep C18 column, eluting with EtOH/(10 mM NaH2PO4 pH 6.7), 50/50. The eluate was diluted, trapped on a C18 Sep-Pak® and eluted with 1 mL EtOH and 9 mL normal saline, then filtered through a 0.22 µm membrane filter. Specific activity and radiochemical purity were determined by analytical HPLC. Results The end-of-synthesis yield of [18F]FPEB was greater with microwave acceleration (10,320 MBq; n = 9) versus thermal heating (7,820 n = 8) and the specific activity was significantly greater (microwave 835 vs thermal 206 GBq/µmol). Radiochemical purity was >98% for both treatments. Overall time of synthesis was shorter by about 15 min for microwave acceleration for a total synthesis time from EOB to EOS of 215 min. Conclusions Microwave acceleration provided [18F]FPEB with higher specific activity and with higher efficiency than thermal heating. Research Support Supported in part by Vanderbilt Dept Radiology