Automated synthesis of [N-methyl-11C]choline, radiopharmaceutical for tumor imaging by PET

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Abstract

An automated method has been developed for the synthesis of [N-methyl-11C]choline, a radiopharmaceutical (RP) for the diagnosis of cancer using positron emission tomography (PET). The synthesis was carried out on a home-made module, using combined technology of on-line 11C-methylation processes and solid-phase extraction methods. The radiochemical yield of [N-methyl-11C]choline was 80% (based on the activity of the methylating agent, [11C]CH3I, decay corrected), which ensures the production of several clinical doses of radiopharmaceutical in one batch. [N-methyl-11C]choline was obtained with a radiochemical purity of more than 99% and an amount of 2-dimethylaminoethanol (the main chemical impurity) of 0.06 mg/mL, which meets the requirements of the Russian and European Pharmacopoeia.

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About the authors

D. D. Vaulina

Bechtereva Institute of the Human Brain, Russian Academy of Sciences

Email: raisa@ihb.spb.ru
Russian Federation, St. Petersburg, 197022

O. F. Kuznetsova

Bechtereva Institute of the Human Brain, Russian Academy of Sciences

Email: raisa@ihb.spb.ru
Russian Federation, St. Petersburg, 197022

V. V. Orlovskaya

Bechtereva Institute of the Human Brain, Russian Academy of Sciences

Email: raisa@ihb.spb.ru
Russian Federation, St. Petersburg, 197022

O. S. Fedorova

Bechtereva Institute of the Human Brain, Russian Academy of Sciences

Email: raisa@ihb.spb.ru
Russian Federation, St. Petersburg, 197022

R. N. Krasikova

Bechtereva Institute of the Human Brain, Russian Academy of Sciences

Author for correspondence.
Email: raisa@ihb.spb.ru
Russian Federation, St. Petersburg, 197022

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Supplementary files

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2. Fig. 1. Display view of a laptop in the synthesis of [11C]choline with comments.

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3. Scheme 1. Synthesis of [11C]choline based on the production of [11C]CH3I by the “wet” method.

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4. Fig. 2. HPLC data for [11C]choline analysis: top – choline standard 7 mg/mL, UV detector (210 nm); bottom – [11C]choline sample being analyzed, γ-detector; X-Bridge C18 column (150 × 4.6 mm), eluent: aqueous solution of 0.1% heptafluorobutyric acid + 2% acetonitrile (v/v), flow rate – 1.5 mL/min.

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5. Fig. 3. HPLC chromatogram of a water sample; X-Bridge C18 column (150 × 4.6 mm), eluent – ​​aqueous solution of 0.1% heptafluorobutyric acid + 2% acetonitrile (v/v), flow rate – 1.5 ml/min; UV 210 nm.

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