Korean Journal of Nuclear Medicine  1999;33(3):298-305

Synthesis of a Dopamine Transporter Imaging Agent, N-(3-18Ffluoropropyl)-2 -carbomethoxy-3 -(4-iodophenyl)nortropane.

Yearn Seong CHOE ; Seung Jun OH ; Dae Yoon CHI ; Sang Eun KIM ; Yong CHOI ; Kyung Han LEE ; Byung Tae KIM

Keywords

Dopamine transporter; Effective specific activity; Positron emission tomography

Country

Republic of Korea

Language

Korean

Abstract

PURPOSE: N-(3-[18F]Fluoroporpy)-2beta- carbomethoxy-3beta-(4-iodophenyl) nortropane ([18F]FP-CIT) has been shown to be very useful for imaging the dopamine transporter. However, synthesis of this radiotracer is some what troublesome. In this study, we used a new method for the preparation of [18F]FP-CIT to increase radiochemical yield and effective specific activity. MATERIALS AND METHODS: [18F]FP-CIT was prepared by N-alkylation of nor-beta-CIT (2 mg) with 3-bromo-l-[18F]fluoropropane in the presence of Et3N (5-6 drops of DMF/CH3CN, 140 degree C, 20 min). 3-Bromo-l-[18F]fluoropropane was synthesized from 5 microliter of 3-bromo-l-trifluoromethanesulfonyloxypropane (3-bromopropyl -l-triflate) and nBu4N18F at 80 degree C. The final compound was purified by reverse phase HPLC and formulated in 13% ethanol in saline. RESULTS: 3-Bromo-l-[18F]fluoropropane was obtained from 3-bromopropyl-l-triflate and nBu4N18F in 77-80% yield. N-Alkylation of nor-beta-CIT with 3-bromo-l-[18F]fluoropropane was carried out at 140 degree C using acetonitrile containing a small volume of DMF as the solvents. The overall yield of [18F]FP-CIT was 5-10% (decay-corrected) with a radiochemical purity higher than 99% and effective specific activity higher than the one reported in the literature based on their HPLC data. The final [18F]FP-CIT solution had the optimal pH (7.0) and it was pyrogen-free. CONCLUSION:: In this study, 3-bromopropyl-l-triflate was used as the precursor for the [18F]fluorination reaction and new conditions were developed for purification of [18F]FP-CIT by HPLC. We established this new method for the preparation of [18F]FP-CIT, which gave high effective specific activity and relatively good yield.