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.
Ishiwata
K
K
Cyclotron and Radioisotope Center, Tohoku University, Sendai.
Yanai
K
K
Iwata
R
R
Takahashi
T
T
Hatazawa
J
J
Itoh
M
M
Watabe
K
K
Watanabe
T
T
Ido
T
T
D000328:Adult; D000368:Aged; D000929:Antidepressive Agents, Tricyclic / Q000097:blood / Q000493:pharmacokinetics*; D001549:Benzamides / Q000097:blood / Q000493:pharmacokinetics*; D001711:Biotransformation; D002250:Carbon Radioisotopes; D002851:Chromatography, High Pressure Liquid; D018492:Dopamine Antagonists / Q000097:blood / Q000493:pharmacokinetics*; D004316:Doxepin / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006634:Histamine H1 Antagonists / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D011485:Protein Binding; D011738:Pyrilamine / Q000097:blood / Q000493:pharmacokinetics*; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D011969:Receptors, Histamine H1 / Q000187:drug effects / Q000378:metabolism; D014055:Tomography, Emission-Computed
D000929:Antidepressive Agents, Tricyclic; D001549:Benzamides; D002250:Carbon Radioisotopes; D018492:Dopamine Antagonists; D006634:Histamine H1 Antagonists; D017448:Receptors, Dopamine D2; D011969:Receptors, Histamine H1; D004316:Doxepin; D011738:Pyrilamine; C030265:nemonapride