Fully automated preparation of [11C]choline and [18F]fluoromethylcholine using TracerLab synthesis modules and facilitated quality control using analytical HPLC.
Modifications of a GE TracerLab FX(C-Pro), which can be implemented for solid-phase [(11)C]methylation are described. The simplified procedure for synthesis of [(11)C]choline uses a single Sep-Pak CM-Light cation-exchange cartridge for both solid-supported reaction and purification. Compared with the commonly used two Sep-Pak method, the low back-pressure of this Sep-Pak enables efficient and reliable production of [(11)C]choline using a TracerLab FX(C-Pro) without requirement for any gas pressure adjustment. Typical radiochemical yields (RCY) are >60%, radiochemical purity (RCP) is 99.9% and levels of residual precursor in the final product, which may inhibit the uptake of [(11)C]choline, are reduced to 1 μg/mL. Similarly, modification of a GE TracerLab FX(FN) is reported which enables gas-phase production of [(18)F]fluoromethylcholine, suitable for pre-clinical use, (in 4-6% RCY and >99.7% RCP) using a related Sep-Pak method. These modifications can be utilized for solid-phase [(11)C]methylation and [(18)F]fluoromethylation of other radiotracers, and allow straightforward switching to other module configurations for solution-phase radiochemistry or loop chemistry. In addition, we report a convenient HPLC ion chromatography method, which can monitor residual precursor and the radiochemical purity of product at the same time, providing highly efficient quality control for routine clinical application. The reported HPLC method is appropriate for analysis of doses of both [(11)C]choline and [(18)F]fluoromethylcholine, and eliminates the need for a GC method to determine residual precursor levels.
Department of Radiology, University of Michigan, Ann Arbor, MI 48109, USA.
Xia
X
Shao
Brian G
BG
Hockley
Raphaël
R
Hoareau
Paul L
PL
Schnau
Peter J H
PJ
Scott
D057205:Automation, Laboratory; D002250:Carbon Radioisotopes; D002794:Choline / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D002851:Chromatography, High Pressure Liquid; D005462:Fluorine Radioisotopes / Q000737:chemistry; D007553:Isotope Labeling / Q000379:methods*; D011786:Quality Control; D019275:Radiopharmaceuticals / Q000138:chemical synthesis
D002250:Carbon Radioisotopes; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; C516370:fluoromethylcholine; D002794:Choline