丙酰-L-肉碱：用碳-11对N-甲基位置进行标记及在大鼠中的药代动力学研究。

Propionyl-L-carnitine: labelling in the N-methyl position with carbon-11 and pharmacokinetic studies in rats.

作者信息

Davenport R J, Law M P, Pike V W, Osman S, Poole K G

机构信息

Cyclotron Unit, Royal Postgraduate Medical School, Hammersmith Hospital, London, U.K.

出版信息

Nucl Med Biol. 1995 Aug;22(6):699-709. doi: 10.1016/0969-8051(95)00010-u.

DOI:10.1016/0969-8051(95)00010-u

PMID:8535330

Abstract

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.

摘要

将正电子发射体碳 -11（半衰期 = 20.4分钟）标记在前瞻性治疗药物丙酰 -L -肉碱的N -甲基位置上，目的是使用正电子发射断层扫描（PET）研究其在人体中的药代动力学。标记是通过在乙醇中，在1,2,2,6,6 -五甲基哌啶存在的情况下，用无载体添加的[11C]碘甲烷（由回旋加速器产生的[11C]二氧化碳制备）对盐酸去甲丙酰 -L -肉碱进行甲基化来实现的。在强阳离子交换柱上对反应混合物进行高效液相色谱（HPLC）分析，以62%的放射化学产率（从[11C]碘甲烷衰变校正）得到高纯度的[N -甲基 -11C]丙酰 -L -肉碱，在放射性核素生产结束后35分钟内即可用于静脉注射。将[N -甲基 -11C]丙酰 -L -肉碱静脉注射给大鼠后，它能迅速从血浆中清除。观察到放射性缓慢摄取到心肌和横纹肌中。在血浆中，未变化的示踪剂在2.5分钟时占放射性的84%，在60分钟时占2.5%。在心脏中，未变化的示踪剂在2.5分钟时占放射性的18%，在15分钟时占2.4%。在血浆和心脏中检测到的其余放射性被鉴定为[N -甲基 -11C]L -肉碱和[N -甲基 -11C]乙酰 -L -肉碱。