Abstract
Positron emission tomography (PET) uses many tracers labeled with fluorine-18 (t 1/2 = 109.8 min; β+ 97%) for quantitative imaging of biochemical and physiological processes in animal and human subjects. In PET methodology, the radioactivity in a dose of an 18F-labeled tracer to be administered to a living subject is measured with a calibrated ionization chamber. This type of detector measures the radioactivity of a sample relative to those of certified amounts of longer-lived surrogate isotopes that are recommended for detector calibration. No alternative means for corroborating widely varying fluorine-18 radioactivity measurements from calibrated ionization chambers has been available. Here, we describe an independent nonradiometric method for this purpose. In this method, highly sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) is used to quantify the relative masses of the radioactive isotopologue ([18F]1) and the accompanying nonradioactive counterpart (carrier 1) in an 18F-labeled tracer preparation to give the mole ratio of [18F]1. High-performance liquid chromatography (HPLC) with a mass-calibrated absorbance detection is used alongside to provide a separate measurement of the aggregate mass of all isotopologues. The radioactivity of the radiotracer is then derived in becquerels (Bq) from these two measurements, plus Avogadro's number and the decay constant of fluorine-18. For the chosen example [18F]LSN3316612, the radioactivity values determined nonradiometrically and with a selected ionization chamber were in fair agreement. In addition, LC-MS/MS alone was found to provide an accurate measure of the half-life of fluorine-18.