Coveney J R, Robbins M S
Pharmacology and Toxicology Research, Mallinckrodt, Inc., Hazelwood, MO 63042.
J Nucl Med. 1987 Dec;28(12):1881-7.
Technetium-99m (99mTc) mercaptoacetylglycylglycylyglycine (MAG3) in high (greater than or equal to 95%) radiochemical purity is prepared from lyophilized kits containing benzoylMAG3, sodium tartrate, lactose, and stannous chloride by adding sodium [99mTC]pertechnetate and heating the contents briefly. Constant-infusion renal whole-blood clearance obtained with [99mTc] MAG3 kits was compared with that obtained with high performance liquid chromatography (HPLC) pure [99mTc]MAG3 and with co-infused iodine-131 (131I) iodohippurate (OIH) in anesthetized rats. Average renal whole-blood clearance of [99mTc]MAG3 from kits was 3.9 +/- 0.4 ml/min/100 g body weight (mean +/- s.e.m. n = 5) and that for HPLC-pure [99mTc]MAG3 was 4.6 +/- 0.3 (n = 3). Renal whole-blood clearance ratios for [99mTc]MAG3 to co-infused iodine-131 (131I) OIH were greater than unity for both kit formulation (1.7 +/- 0.1) and HPLC-pure [99mTc]MAG3 (1.9 +/- 0.2). Differences in these two measures were not significant. Plasma binding (determined from blood drawn at the end of the infusion) of [99mTc]MAG3 prepared from both kits (75 +/- 2%, n = 4) and HPLC-separation (76 +/- 4%) were greater than that of [131I]OIH in corresponding plasma samples (31 +/- 1% and 32 +/- 2%) respectively). Renograms performed in anesthetized rats revealed no statistically significant differences between kit-prepared [99mTc]MAG3 and [131I]OIH in terms of time-to-peak renal activity (5.0 +/- 1.7 min, n = 6; and 2.2 +/- 0.2 min, n = 3, mean +/- s.e.m. for [99mTc]MAG3 and [131I]OIH, respectively), in terms of time to fall to half-maximal activity (15.3 +/- 2.4 min and 9.6 +/- 2.1 min, respectively), or in terms of fraction of peak radioactivity in right kidney (0.53 +/- 0.01 for both substances). To assess possible interference from hepatobiliary uptake and excretion in renal failure, radioactivity in liver regions of interest was followed by gamma camera scintigraphy for 30 min after intravenous injection of [131I]OIH and kit and HPLC-purified [99mTc]MAG3 in anesthetized rats rendered anephric by ligating renal peduncles. Liver activity was 25% of total for both preparations of [99mTc]MAG3 and was 22% of total for [131I]OIH. There were no significant differences among the substances.
通过向含有苯甲酰MAG3、酒石酸钠、乳糖和氯化亚锡的冻干药盒中加入高锝[99mTc]酸钠并短暂加热内容物，制备放射化学纯度高（大于或等于95%）的锝-99m（99mTc）巯基乙酰甘氨酰甘氨酰甘氨酸（MAG3）。将用[99mTc]MAG3药盒获得的恒速输注肾全血清除率与用高效液相色谱（HPLC）纯的[99mTc]MAG3以及与在麻醉大鼠中共输注的碘-131（131I）碘马尿酸（OIH）获得的肾全血清除率进行比较。药盒中[99mTc]MAG3的平均肾全血清除率为3.9±0.4 ml/min/100 g体重（均值±标准误，n = 5），HPLC纯的[99mTc]MAG3的平均肾全血清除率为4.6±0.3（n = 3）。对于药盒制剂（1.7±0.1）和HPLC纯的[99mTc]MAG3（1.9±0.2），[99mTc]MAG3与共输注的碘-131（131I）OIH的肾全血清除率比值均大于1。这两种测量方法的差异不显著。两种药盒制备的[99mTc]MAG3（75±2%，n = 4）和HPLC分离的[99mTc]MAG3（76±4%）在输注结束时从采集的血液中测定的血浆结合率分别高于相应血浆样本中[131I]OIH的血浆结合率（31±1%和32±2%）。在麻醉大鼠中进行的肾图显示，药盒制备的[99mTc]MAG3和[131I]OIH在达到肾活性峰值的时间（分别为5.0±1.7分钟，n = 6；和2.2±0.2分钟，n = 3，[99mTc]MAG3和[131I]OIH的均值±标准误）、降至最大活性一半的时间（分别为15.3±2.4分钟和9.6±2.1分钟）或右肾峰值放射性分数（两种物质均为0.53±0.01）方面均无统计学显著差异。为了评估肾衰竭时肝胆摄取和排泄的可能干扰，在通过结扎肾蒂使麻醉大鼠无肾后，静脉注射[131I]OIH、药盒和HPLC纯化的[99mTc]MAG3后，用γ相机闪烁扫描术跟踪感兴趣的肝脏区域的放射性30分钟。两种[99mTc]MAG3制剂的肝脏活性均为总量的25%，[131I]OIH的肝脏活性为总量的22%。这些物质之间无显著差异。
