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

Although [F-18] tluoropropylcarbomethoxyiodophenylnortropane (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 [F-18]FP-CIT in single-step manual and automatic preparation procedures. [F-18]F- was trapped on a QMA Sep-Pak cartridge or PS-HCO3 cartridge and eluted with Cs2CO3/K-222 buffer or TBAHCO(3), respectively, or 8 mu l of TBAOH was added directly to [F-18]F-/(H2O)-O-18 solution in a reactor without using a cartridge. After drying, [F-18] fluorination was performed with 2-6 mg of mesylate precursor, 100 mu l of CH3CN and 500 mu l of t-BuOH at 50-120 degrees 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 degrees C and 20 min of [F-18] fluorination (n = 3). We obtained low radiochemical yields of [F-18]FP-CIT with carbonate elution systems such as Cs2CO3 or TBAHCO(3). 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 [F-18]FP-CIT using a protic solvent system. This method gave a high radiochemical yield with high reproducibility and might enable [F-18]FP-CIT to be used clinically and commercially. (c) 2007 Elsevier Inc. All rights reserved.