11C-MePPEP

A fast and sensitive liquid chromatographic (fast-LC) method with radiometric detection was developed and validated to analyze positron emission tomography (PET) radioligands in plasma during PET studies. The plasma samples were deproteinized with acetonitrile and the extracts were injected into the fast-LC system coupled to an on-line radioactivity detector. Under the optimum conditions, complete separation of target PET radioligands from their radioactive metabolites was achieved within the short run time of only 3.5-min. The limits of detection were 1.0-1.2 Becquerel (Bq) for (11)C and (18)F-labeled compounds. This method can successfully be applied to study the metabolism of a wide variety of PET radioligands in human and monkey plasma with higher numbers of samples to be analyzed compared to the traditional LC method.

Determination of radio-metabolites in plasma samples taken during a positron emission tomography (PET) study is an important component in the pharmacokinetic evaluation of PET radioligands. We have developed and validated a new analytical procedure for the plasma metabolite analysis of PET radioligands based on micellar liquid chromatography using an anionic surfactant mobile phase. Chromatographic separation was performed on an octadecyl semipreparative column (10 mm I.D. × 160 mm, 10 μm) using 100 mM sodium dodecyl sulfate (SDS) and 1-butanol in 10 mM sodium-phosphate (pH 7.2) at a flow rate of 5 mL/min. The samples taken from monkey or human plasma during PET measurements were directly injected into a liquid chromatographic (LC) system coupled to an online radiometric detector under micellar conditions using 1-2% (v/v) 1-butanol mobile phase to remove plasma proteins and concentrate the analytes at the column head. At 2 min, mobile phase was changed to elute and separate PET radioligand and its radiometabolites with high peak capacity under high submicellar conditions (10-25% 1-butanol). This procedure allowed direct plasma injection (up to 2 mL) into the LC column without any pretreatment with a short analysis-time of 8-10 min. Satisfactory reproducibility, linearity, sensitivity, accuracy and recovery were obtained in the validation study. The developed method was successfully applied to study the metabolism for diverse groups of PET radioligands and provided reliable determination of PET radioligands in human and monkey plasma. This method is advantageous in terms of simplifying and shortening the processes required to analyze short-lived radioligands as well as in providing a more accurate estimation of the metabolite corrected input function, especially for the radioligands with lower recoveries or degradation potential during the deproteination process in a conventional procedure.