心肌灌注显像剂~(99)Tc~m-Q_3的制备方法学和药代动力学研究

THE RESEARCH OF PREPARING METHODOLOGY AND PHARMACOKINETICS FOR A NOVEL MYOCARDIAL PERFUSION IMAGING AGENT 99 Tc m\|Q\-3

  • 摘要: 采用正交实验筛选法制备99 Tcm  Q3 (99 Tcm  N, N亚乙基二(乙酰丙酮亚胺)二三(3甲氧基1丙基)膦);家兔注射99 Tcm  Q3 后定时采血,绘制血药时间放射性曲线并分析其体内药代动力学。结果显示,制备99 Tcm  Q3 的最佳配方为 K O H 溶液(1 m ol/ L,溶于 50% 乙醇)30 μ L、 Sn Cl2·2 H2 O 溶液(2 g/ L,溶于无水乙醇)20 μ L、 N, N′亚乙基二(乙酰丙酮亚胺)20 m g 和三(2甲氧基1丙基)膦5 m g。这些因素对标记物放化纯度的影响均具有显著性差异( P< 0.01),且各因素间不存在交互作用。99 Tcm  Q3 兔血清除动力学符合一次静脉给药的二室药代动力学模型,并且99 Tcm  Q3 血浆蛋白结合率低((7.13±0.42)% ))。

     

    Abstract: The preparing methodology and pharmacokinetics of myocardial perfusion imaging agent 99 Tc m\|Q\-3 are studied. The optimum scheme of 99 Tc m labelling on the basis of exploring the effects of varied labelled condition on radiochemical purity is established by multivariate orthogonal experimental design. The pharmacokinetics is investigated in rabbits, and the plasma protein binding rate is also measured. “30 μL of 1 mol/L KOH in 50% ethanol, 20 μL of 2 g/L SnCl\-2·2H\-2O in degassed ethanol, 20 mg of N,N′\|ethylene\|bis (acetylacetone iminato) and 5 mg of tris (3\|methoxy\|1\|propyl) phosphine” are chosen as the optimum scheme of this labelled complex. Each of the factors exists significant effect on the radiochemical purity and there is no one\|class cross effect on the radiochemical purity between them. The pharmacokinetics of 99 Tc m\|Q\-3 conform to two\|compartment model with 0.23 ±0.09 mL/min of excelent blood clearence, an initial half\|time of 1.6±0.4 min and a late half time of 203.0±25.8 min. In vitro protein binding rate is lower.\;

     

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