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

Jan Wenz; Felix Arndt; Samuel Samnick

doi:10.1186/s41181-022-00159-y

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

EJNMMI Radiopharm Chem. 2022 Mar 28;7(1):6. doi: 10.1186/s41181-022-00159-y.

Authors

Jan Wenz¹, Felix Arndt², Samuel Samnick²

Affiliations

¹ Department of Nuclear Medicine, Interdisciplinary PET Center, Universitätsklinikum Würzburg, Oberdürrbacher Strasse 6, 97080, Würzburg, Germany. Wenz_J@ukw.de.
² Department of Nuclear Medicine, Interdisciplinary PET Center, Universitätsklinikum Würzburg, Oberdürrbacher Strasse 6, 97080, Würzburg, Germany.

Abstract

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-[¹¹C]choline, L-S-methyl-[¹¹C]methionine and [¹¹C]acetate.

Results: The target gas purification of cyclotron produced [¹¹C]CO₂ and subsequent conversion to [¹¹C]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-[¹¹C]choline and L-S-methyl-[¹¹C]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 [¹¹C]MeI. After 18 min N-methyl-[¹¹C]choline was isolated with 52% decay corrected yield and a radiochemical purity of > 99%. For L-S-methyl-[¹¹C]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 [¹¹C]acetate synthesis. The disposable unit was filled with 1 mL MeMgCl (0.75 M) in tetrahydrofuran (THF) bevore [¹¹C]CO₂ was passed through. After complete release of [¹¹C]CO₂ 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 [¹¹C]CO₂ before dispensing. Under these conditions the total reaction time was 18 ± 2 min and pure [¹¹C]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-[¹¹C]choline, L-S-methyl-[¹¹C]methionine and [¹¹C]acetate.

Keywords: Carbon-11; Carboxylation; Isotopes; Isotopic labelling; Methylation; Radiochemistry; Radiopharmaceuticals.