A new concept for the production of (11)C-labelled radiotracers

BACKGROUND: The GMP-compliant production of radiopharmaceuticals has been performed using disposable units (cassettes) with a dedicated synthesis module. To expand this “plug ‘n’ synthesize” principle to a broader scope of modules we developed a pressure controlled setup that offers an alternative to the usual stepper motor controlled rotary valves. The new concept was successfully applied to the synthesis of N-methyl-[(11)C]choline, L-S-methyl-[(11)C]methionine and [(11)C]acetate. RESULTS: The target gas purification of cyclotron produced [(11)C]CO(2) and subsequent conversion to [(11)C]MeI was carried out on a TRACERlab Fx C Pro module. The labelling reactions were controlled with a TRACERlab Fx FE module. With the presented modular principle we were able to produce N-methyl-[(11)C]choline and L-S-methyl-[(11)C]methionine by loading a reaction loop with neat N,N'-dimethylaminoethanol (DMAE) or an ethanol/water mixture of NaOH and L-homocysteine (L-HC), respectively and a subsequent reaction with [(11)C]MeI. After 18 min N-methyl-[(11)C]choline was isolated with 52% decay corrected yield and a radiochemical purity of > 99%. For L-S-methyl-[(11)C]methionine the total reaction time was 19 min reaction, yielding 25% of pure product (> 97%). The reactor design was used as an exemplary model for the technically challenging [(11)C]acetate synthesis. The disposable unit was filled with 1 mL MeMgCl (0.75 M) in tetrahydrofuran (THF) bevore [(11)C]CO(2) was passed through. After complete release of [(11)C]CO(2) the reaction mixture was quenched with water and guided through a series of ion exchangers (H(+), Ag(+) and OH(−)). The product was retained on a strong anion exchanger, washed with water and finally extracted with saline. The product mixture was acidified and degassed to separate excess [(11)C]CO(2) before dispensing. Under these conditions the total reaction time was 18 ± 2 min and pure [(11)C]acetate (n = 10) was isolated with a decay corrected yield of 51 ± 5%. CONCLUSION: Herein, we described a novel single use unit for the synthesis of carbon-11 labelled tracers for preclinical and clinical applications of N-methyl-[(11)C]choline, L-S-methyl-[(11)C]methionine and [(11)C]acetate. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s41181-022-00159-y.