PROPIONYL-L-CARNITINE - LABELING IN THE N-METHYL POSITION WITH C-11 AND PHARMACOKINETIC STUDIES IN RATS

The prospective therapeutic, propionyl-L-carnitine, was labelled in th e N-methyl position with the positron emitter, carbon-11 (t(1/2) = 20. 4 min), with a view to studying its pharmacokinetics in humans using P ET. Labelling was achieved by methylating nor-propionyl-L-carnitine hy drochloride with no-carrier-added [C-11]iodomethane (produced from cyc lotron-produced [C-11]carbon dioxide) in ethanol in the presence of 1, 2,2,6,6-pentamethylpiperidine. HPLC of the reaction mixture on a stron g cation exchange column provided high purity [N-methyl-C-11]propionyl -L-carnitine in 62% radiochemical yield (decay-corrected from [C-11]io domethane), ready for intravenous administration within 35 min from th e end of radionuclide production. [N-methyl-C-11]propionyl-L-carnitine , given intravenously to rats, cleared rapidly from plasma. A slow upt ake of radioactivity into myocardium and striated muscle was observed. In plasma, unchanged tracer represented 84% of the radioactivity at 2 .5 min and 2.5% of the radioactivity at 60 min. In heart, unchanged tr acer represented 18% of radioactivity at 2.5 min and 2.4% at 15 min. T he remainder of radioactivity detected in plasma and heart was identif ied as [N-methyl-C-11]L-carnitine and [N-methyl-C-11]acetyl-L-carnitin e.