[11C]sarcosine for PET imaging of prostate cancer

Objectives Tissue levels of sarcosine (2-(methylamino)ethanoic acid) have been found to be elevated in localized prostate cancer compared to benign prostatic tissues by metabolomic profiling and mass spectrometry-based target metabolite validation. We have prepared [11C]sarcosine (2-(methyl-11C-amino)ethanoic acid, 1) to evaluate it as a new PET imaging probe. In DU-145 and PC-3 tumor xenografts, and in a human subject with prostate cancer, [11C]sarcosine showed high-contrast images and favorable radiation dosimetry. However, the N-methyl of [11C]sarcosine is demethylated by sarcosine dehydrogenase in vivo, resulting in volatile [11C]CO2. We report here the radiosynthesis of 2-(methylamino)ethanoic-11C acid ([11C]sarcosine, 2). Radiolabeling of sarcosine at the carboxylic acid will allow further investigation of the metabolic and enzymatic function differences in prostate cancer. In addition, the novel carbon-11 labeling technique developed here to add [11C]ethanoic acid to an amine can be used to generate other radioligands and easily be extended to the radiosynthesis of related amides and nitriles.

Methods [11C]HCN precursor was obtained as reported and trapped on a platinum wire coated with NaOH. After removal of excess NH3 the activity was eluted with aqueous NaCN (carrier added) into a vial containing methylamine and formaldehyde. The resulting intermediate was hydrolyzed with 10M NaOH at 100 °C. 2-(methylamino)ethanoic-11C acid was then purified with ion exchange cartridges.

Results [11C]sarcosine, 2 was prepared in a multistep synthesis. Total synthesis time was 40 minutes from end of beam. In non-optimized conditions, total radiochemical yields were 1-3% based on [11C]CO2 (non-decay corrected).

Conclusions Radiolabeling of sarcosine at the carboxylic acid has been achieved for the first time. Further preclinical and clinical studies of this compound are underway. The novel carbon-11 labeling technique of adding [11C]methylene nitrile to an amine can be extensively used to generate other radiopharmaceuticals.