One-step high-radiochemical-yield synthesis of [18F]FP-CIT using a protic solvent system

Although [18F] fluoropropylcarbomethoxyiodophenylnortropane (FP-CIT) is a promising radiopharmaceutical for dopamine transporter imaging, it has not been used for clinical studies because of low radiochemical yield. The purpose of our study was to develop a new radiochemistry method using a protic solvent system to obtain a high radiochemical yield of [18F]FP-CIT in single-step manual and automatic preparation procedures. [18F]F− was trapped on a QMA Sep-Pak cartridge or PS-HCO3 cartridge and eluted with Cs2CO3/K222 buffer or TBAHCO3, respectively, or 8 μl of TBAOH was added directly to [18F]F−/H218O solution in a reactor without using a cartridge. After drying, [18F] fluorination was performed with 2-6 mg of mesylate precursor, 100 μl of CH3CN and 500 μl of t-BuOH at 50-120°C for 5-30 min, followed by high-performance liquid chromatography (HPLC) purification to obtain the final product. For comparison, the same procedure was performed with a tosylate precursor. Manual synthesis gave a decay-corrected radiochemical yield of 52.2±4.5%, and optimal synthesis conditions were as follows: TBAOH addition, 4 mg of precursor, 100°C and 20 min of [18F] fluorination (n=3). We obtained low radiochemical yields of [18F]FP-CIT with carbonate elution systems such as Cs2CO3 or TBAHCO3. We also developed an automatic synthesis method based on manual synthesis results. In automatic production, we obtained a decay-corrected radiochemical yield of 35.8±5.2% after HPLC purification, and we did not have any synthesis failures (n=14). Here, we describe our new method for the synthesis of [18F]FP-CIT using a protic solvent system. This method gave a high radiochemical yield with high reproducibility and might enable [18F]FP-CIT to be used clinically and commercially.