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

Area of Science:

• Biochemistry
• Radiochemistry
• Medical Imaging

Background:

• Glycine N-methyltransferase, overexpressed in some cancers, uses S-adenosyl methionine (SAM) for methylation.
• SAM is crucial for transmethylation reactions, making [11C]SAM a potential PET imaging agent for tumors.
• Existing enzymatic synthesis of [11C]SAM is limited; a novel chemical approach is needed.

Purpose of the Study:

• To develop and optimize a new, one-pot chemical synthesis for the radiotracer [11C]SAM.
• To evaluate the quality, stability, and properties of the synthesized [11C]SAM for potential use in cancer imaging.

Main Methods:

• Optimization of [11C]SAM synthesis using an automated module, varying methylating agent, precursor, temperature, and time.
• Purification via semipreparative HPLC.
• Assessment of radiochemical stability, lipophilicity (Log P), and plasma protein binding.

Main Results:

• Optimal synthesis achieved using [11C]CH3OTf and 5 mg precursor in formic acid at 60°C for 1 minute.
• [11C]SAM produced as a diastereomeric mixture (53:47 ratio) meeting quality control specifications.
• The radiotracer demonstrated stability in formulation and plasma, with low lipophilicity and plasma protein binding.

Conclusions:

• A novel, optimized chemical method for [11C]SAM production has been established.
• The synthesized [11C]SAM meets quality standards and exhibits favorable in vitro stability.
• This radiotracer is suitable for preclinical and clinical evaluation in assessing transmethylation activity.