GMP compliant simplified fast and high yielding automated synthesis of [18F]Fallypride without the need of HPLC purification
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Background [ 18 F]Fallypride PET has been used to study D2/3 receptor occupancy and density in neuropsychiatric disorders including Huntington’s disease (HD) and aging in humans. Nevertheless, the various synthetic methods including those provided by commercial synthesizers for [ 18 F]Fallypride exhibit a disadvantage concerning the necessity using a HPLC purification step, which causes difficulties in the automation, leads to long synthesis times and moderate yields. Therefore utilizing the purification step by SPE cartridges is considered highly desirable for future commercialization of radiopharmaceutical cassettes. In our lab we have developed a simplified reliable automatic radio synthesis of [ 18 F]Fallypride by using SPE cartridges for the purification step without the need of HPLC. Results A simplified radio synthesis of [ 18 F]Fallypride has been developed without the use of HPLC for both a commercial cassette based synthesis system (AllinOne (AiO) system, Trasis, Belgium) and a research synthesis module with fixed tubing (RNplus, Synthra, Germany). The cleaning step involves a serial combination of several SPE cartridges. The synthesis time was shortened by 44% compared to synthesis using HPLC. At the same time the not decay corrected yield increases from 44% to 59% by using TBAHCO 3 as phase transfer catalysts and from 17% to 31% for the synthesis with K 2 CO 3 /Kryptofix-[2.2.2] compared to synthesis using HPLC. The radio chemical purity was always >98% and all quality control parameters (e.g. sterility, endotoxin, stability and radio chemical purity) were conform to the European Pharmacopoeia. Conclusions A GMP compliant automatic synthesis of [ 18 F]Fallypride including purification using simple solid phase extraction cartridges instead of HPLC was developed and evaluated. The implementation of the simplified synthesis in both used commercial modules allows efficient and reproducible radio synthesis of [ 18 F]Fallypride and leads to short synthesis times and high radiochemical yields with high radiochemical purity.
