title: One-step high-radiochemical-yield synthesis of [18F]FP-CIT using a protic solvent system.
abstract: 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-HCO(3) cartridge and eluted with Cs2CO(3)/K222 buffer or TBAHCO3 respectively, or 8 microl of TBAOH was added directly to [18F]F(-)/H(2)(18)O solution in a reactor without using a cartridge. After drying, 18F] fluorination was performed with 2-6 mg of mesylate precursor, 100 microl of CH(3)CN and 500 microl 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 [18F] fluorination (n=3). We obtained low radiochemical yields of [18F]FP-CIT with carbonate elution systems such as Cs2CO(3) 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.
authors.affiliation: Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, South Korea.
authors.forename: Sang Ju
authors.initials: SJ
authors.lastname: Lee
authors.forename: Seung Jun
authors.initials: SJ
authors.lastname: Oh
authors.forename: Dae Yoon
authors.initials: DY
authors.lastname: Chi
authors.forename: Se Hun
authors.initials: SH
authors.lastname: Kang
authors.forename: Hee Seup
authors.initials: HS
authors.lastname: Kil
authors.forename: Jae Seung
authors.initials: JS
authors.lastname: Kim
authors.forename: Dae Hyuk
authors.initials: DH
authors.lastname: Moon
mesh_terms: D001331:Automation; D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D005462:Fluorine Radioisotopes / Q000737:chemistry; D007202:Indicators and Reagents; D007553:Isotope Labeling; D011786:Quality Control; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000302:isolation & purification; D012997:Solvents; D014326:Tropanes / Q000138:chemical synthesis* / Q000302:isolation & purification
chemical_list: D005462:Fluorine Radioisotopes; D007202:Indicators and Reagents; D019275:Radiopharmaceuticals; D012997:Solvents; D014326:Tropanes; C087552:2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane