Characterization of fast-decaying PET radiotracers solely through LC-MS/MS of constituent radioactive and carrier isotopologues

The LC-MS/MS was tuned and set up with methods to generate and measure the product ions specific for carbon-11 species and M？+？1 carrier (predominantly the carbon-13 isotopologue) in four 11C-labeled tracers. These radiotracers were synthesized and then analyzed before extensive carbon-11 decay. The peak areas of carbon-11 species and M？+？1 carrier from the LC-MS/MS measurement and the calculated abundances of carbon-12 carrier and M？+？1 radioactive species gave the mole fraction of carbon-11 species in each sample. This value upon multiplication with the theoretical specific radioactivity of carbon-11 gave the specific radioactivity of the radiotracer.LC-MS/MS of each 11C-labeled tracer generated the product ion peaks for carbon-11 species and M？+？1 carrier at the expected LC retention time. The intensity of the radioactive peak diminished as time elapsed and was undetectable after six half-lives of carbon-11. Measurements of radiotracer-specific radioactivity determined solely by LC-MS/MS at timed intervals gave a half-life for carbon-11 (20.43 min) in excellent agreement with the value obtained radiometrically. Additionally, the LC-MS/MS measurement gave specific radioactivity values (83 to 505 GBq/μmol) in good agreement with those from conventional radiometric methods.11C-Labeled tracers were characterized at a fundamental level involving isolation and mass detection of extremely low-abundance carbon-11 species along with the M？+？1 carrier counterpart. This LC-MS/MS method for characterizing fast-decaying radiotracers is valuable in both the development and production of PET radiopharmaceuticals.Positron-emission tomography (PET), as an expanding biomedical research and diagnostic imaging technique, relies on the use of radiotracers labeled with a positron emitter, often either carbon-11 (t1/2？=？20.38 min) or fluorine-18 (t1/2？=？109.7 min) [1-3]. The short physical half-lives of these radiotracers demand rapid techniques for establishing the quality of each pro