A high yielding one-pot synthesis of [18F]fluoromethylcholine

1149 Objectives Demand for [18F]fluoromethylcholine ([18F]FCH) continues to grow in the United States. However, in our laboratory, the traditional method of preparing [18F]FCH via methylation of dimethylaminoethanol (DMAE) with [18F]fluorobromomethane has proven problematic, hampered by low yields (≤4%) and high residual DMAE contamination (≤1 mg/mL). To address these issues, we have developed a one-pot approach for preparing [18F]FCH via in situ formation of [18F]fluoromethyl tosylate ([18F]FCH2OTs). Methods [18F]Fluoride was trapped on a QMA cartridge and eluted with K2CO3. Kryptofix-222 was added and the azeotropic water/acetonitrile mixture was evaporated to dryness. Methylene ditosylate (7 mg) in MeCN (750 µL) and water (10 µL) was added and the reaction heated at 120°C for 10 min to generate [18F]FCH2OTs. The reaction mixture was cooled to 60°C and DMAE (40 µL in 350 µL MeCN) was added. The reactor was heated at 120°C for an additional 10 min., cooled to 60°C and the reaction solvent was evaporated. The reaction mixture was diluted with water (5.5 mL) and passed through a C18 sep-pak cartridge into a round-bottomed flask charged with ethanol (10 mL). The procedure was repeated with additional water (5.5 mL) to rinse the reactor, and the resulting water-ethanol mixture was passed through a CM sep-pak cartridge. [18F]FCH was trapped on the CM cartridge, and the cartridge was flushed with ethanol (15 mL) to remove residual DMAE, rinsed with water (20 mL) to remove excess ethanol, before final elution of [18F]FCH with USP saline. The formulated product was passed through a 0.22 µm filter into a sterile dose vial, and submitted for QC testing. Results Typical yields of [18F]FCH were 91 mCi (7% non-decay-corrected based upon ~1.3 Ci [18F]fluoride). Doses passed all quality control tests (Table), confirming their suitability for clinical PET imaging. Conclusions A one-pot synthesis of [18F]fluoromethylcholine has been developed. The synthesis is high yielding, and doses contain extremely low levels of residual DMAE. Research Support Financial support by NIBIB (T32EB005172-02) is gratefully acknowledged.