Propionyl-L-carnitine: labelling in the N-methyl position with carbon-11 and pharmacokinetic studies in rats.
The prospective therapeutic, propionyl-L-carnitine, was labelled in the N-methyl position with the positron-emitter, carbon-11 (t1/2 = 20.4 min), with a view to studying its pharmacokinetics in humans using PET. Labelling was achieved by methylating nor-propionyl-L-carnitine hydrochloride with no-carrier-added [11C]iodomethane (produced from cyclotron-produced [11C]carbon dioxide) in ethanol in the presence of 1,2,2,6,6-pentamethylpiperidine. HPLC of the reaction mixture on a strong cation exchange column provided high purity [N-methyl-11C]propionyl-L-carnitine in 62% radiochemical yield (decay-corrected from [11C]iodomethane), ready for intravenous administration within 35 min from the end of radionuclide production. [N-methyl-11C]Propionyl-L-carnitine, given intravenously to rats, cleared rapidly from plasma. A slow uptake 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 tracer represented 18% of radioactivity at 2.5 min and 2.4% at 15 min. The remainder of radioactivity detected in plasma and heart was identified as [N-methyl-11C]L-carnitine and [N-methyl-11C]acetyl-L-carnitine.
Cyclotron Unit, Royal Postgraduate Medical School, Hammersmith Hospital, London, U.K.
R J
RJ
Davenport
M P
MP
Law
V W
VW
Pike
S
S
Osman
K G
KG
Poole
D000818:Animals; D001711:Biotransformation; D002250:Carbon Radioisotopes; D002316:Cardiotonic Agents / Q000378:metabolism / Q000493:pharmacokinetics*; D002331:Carnitine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D017357:Cyclotrons; D007553:Isotope Labeling / Q000379:methods; D008099:Liver / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014018:Tissue Distribution
D002250:Carbon Radioisotopes; D002316:Cardiotonic Agents; C003223:propionylcarnitine; D002331:Carnitine