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

Nucl Med Biol. 2007 May;34(4):345-51. doi: 10.1016/j.nucmedbio.2007.02.007.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Automation
  • Catalysis
  • Chromatography, High Pressure Liquid
  • Chromatography, Thin Layer
  • Fluorine Radioisotopes / chemistry
  • Indicators and Reagents
  • Isotope Labeling
  • Quality Control
  • Radiopharmaceuticals / chemical synthesis*
  • Radiopharmaceuticals / isolation & purification
  • Solvents
  • Tropanes / chemical synthesis*
  • Tropanes / isolation & purification


  • Fluorine Radioisotopes
  • Indicators and Reagents
  • Radiopharmaceuticals
  • Solvents
  • Tropanes
  • 2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane