Hume S P, Brown D J, Ashworth S, Hirani E, Luthra S K, Lammertsma A A
PET Methodology Group, Hammersmith Hospital, London, UK.
J Neurosci Methods. 1997 Sep 5;76(1):45-51. doi: 10.1016/s0165-0270(97)00078-2.
When estimated in vitro, the parameters which describe the binding of radiolabelled analogues of cocaine to sites on the dopamine transporter are very much influenced by the methodology used. In the present study, a small animal positron emission tomography (PET) scanner was used to estimate in vivo saturation kinetics for two carbon-11 labelled compounds presently used to monitor dopamine terminal function. The binding of [11C]CFT (WIN 35,428) in rat striatum was adequately described by a single-site model, giving an apparent dissociation constant corresponding to an intravenous dose of 242 nmol/kg. In contrast, the binding of [11C]RTI-121 was better described by a two-site model with the 'high-affinity' site or state (dissociation constant = 1 nmol/kg) being significantly occupied at doses routinely used in PET scanning. Such findings cannot readily be predicted from in vitro work, but could aid in both the choice of ligand and the model used in quantification of scan data. While multi-dose in vivo PET studies are difficult in man, rat PET can easily be employed either pre-clinically for putative radioligands, or experimentally, to study drug interactions and receptor occupancy related to functional efficacy.
在体外进行估算时，描述可卡因放射性标记类似物与多巴胺转运体上位点结合的参数会受到所用方法的很大影响。在本研究中，使用小动物正电子发射断层扫描（PET）扫描仪来估算目前用于监测多巴胺终末功能的两种碳-11标记化合物的体内饱和动力学。[11C]CFT（WIN 35,428）在大鼠纹状体中的结合情况可用单一位点模型充分描述，得出的表观解离常数对应于242 nmol/kg的静脉注射剂量。相比之下，[11C]RTI-121的结合情况用双位点模型能更好地描述，在PET扫描常规使用的剂量下，“高亲和力”位点或状态（解离常数 = 1 nmol/kg）会被显著占据。这样的发现难以从体外研究中轻易预测，但有助于配体的选择以及用于扫描数据定量的模型。虽然在人体中进行多剂量体内PET研究很困难，但大鼠PET在临床前可轻松用于推定放射性配体，或在实验中用于研究与功能疗效相关的药物相互作用和受体占有率。
