Analysis of plasma metabolites during human PET studies with three receptor ligands, [¹¹C]YM-09151-2, [¹¹C]doxepin and [¹¹C]pyrilamine

Carbon-11 labeled metabolites in human plasma were analyzed by high-performance liquid chromatography during positron emission tomography (PET) studies using the dopamine D₂ ligand [¹¹C] YM-09151-2 as well as the histamine H₁ ligands [¹¹C]doxepin and [¹¹C]pyrilamine. For all the three tracers, blood clearance of the radioactivity was extremely rapid after an i.v. injection. The plasma protein-binding of [¹¹C]YM-09151-2 and [¹¹C]doxepin had protective effects upon the metabolic alteration of the ligands, whereas [¹¹C]pyrilamine was free from the protein-binding and immediately degraded. The degradation of [¹¹C]doxepin was more rapid in epileptic patients on medication than in normal subjects. These results indicate that analysis of metabolites in the plasma is necessary to determine the accurate arterial input function for quantitative PET measurement.