Automated One-pot Radiosynthesis of [11C]S-adenosyl Methionine.

Abstract

Background: Glycine N-methyltransferase is an enzyme overexpressed in some neo-plastic tissues. It catalyses the methylation of glycine using S-adenosyl methionine (SAM or AdoM-et) as substrate. SAM is involved in a great variety of biochemical processes, including transmeth-ylation reactions. Thus, [11C]SAM could be used to evaluate transmethylation activity in tumours. The only method reported for [11C]SAM synthesis is an enzymatic process with several limitations. We propose a new chemical method to obtain [11C]SAM, through a one-pot synthesis.Method: The optimization of [11C]SAM synthesis was carried out in the automated TRACERlab® FX C Pro module. Different labelling conditions were performed varying methylating agent, precur-sor amount, temperature and reaction time. The compound was purified using a semi-preparative HPLC. Radiochemical stability, lipophilicity and plasma protein binding were evaluated.Results: The optimum labelling conditions were [11C]CH3OTf as the methylating agent, 5 mg of precursor dissolved in formic acid at 60 ºC for 1 minute. [11C]SAM was obtained as a diastereomer-ic mixture. Three batches were produced and quality control was performed according to specifica-tions. [11C]SAM was stable in final formulation and in plasma. Log POCT obtained for [11C]SAM was (-2,01 ± 0,07) (n=4), and its value for plasma protein binding was low.Conclusion: A new chemical method to produce [11C]SAM was optimized. The radiotracer was ob-tained as a diastereomeric mixture with a 53:47 [(R,S)-isomer: (S,S)-isomer] ratio. The compound was within the quality control specifications. In vitro stability was verified. This compound is suita-ble to perform preclinical and clinical evaluations.