Florencia Zoppolo, Williams Porcal, Patricia Oliver, Eduardo Savio* and Henry Engler Pages 203 - 211 ( 9 )
Background: Glycine N-methyltransferase is an enzyme overexpressed in some neoplastic tissues. It catalyses the methylation of glycine using S-adenosyl methionine (SAM or AdoMet) as substrate. SAM is involved in a great variety of biochemical processes, including transmethylation 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, precursor amount, temperature and reaction time. The compound was purified using a semipreparative 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 °C for 1 minute. [11C]SAM was obtained as a diastereomeric mixture. Three batches were produced and quality control was performed according to specifications. [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 obtained 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 suitable to perform preclinical and clinical evaluations.
S-adenosyl methionine, Glycine N-methyltransferase, 11C[SAM], PET radiotracers, radiochemistry, 11C-labelling, automated synthesis.
Uruguayan Centre of Molecular Imaging (CUDIM), Montevideo, Uruguayan Centre of Molecular Imaging (CUDIM), Montevideo, Uruguayan Centre of Molecular Imaging (CUDIM), Montevideo, Ricaldoni 2010, Postal Code 11.600, Montevideo, Uruguayan Centre of Molecular Imaging (CUDIM), Montevideo