Department of Radiology, Thomas Jefferson University, Philadelphia, PA, USA.
Int J Toxicol. 2010 Jan-Feb;29(1):32-9. doi: 10.1177/1091581809354342. Epub 2009 Dec 14.
Gas-filled microbubbles are used as contrast agents in diagnostic ultrasound imaging. A preclinical, acute toxicity study of 2 surfactant-stabilized ultrasound contrast agents (ST68 and ST44) was conducted. Subjects were 104 Sprague-Dawley rats (experimental doses, 0.1, 0.2, 0.8, and 1.0 mL/kg; control, 1.0 mL/kg saline) that were studied for 14 days after contrast; clinical signs, weight, blood, and urine were evaluated. Histopathology was performed following euthanasia. Of the 40 animals receiving ST44, 4 died prematurely and a dose dependency was demonstrated (P = .011), whereas in the ST68 groups only 1 death occurred (no dose dependency; P = .48). Only the weight of rats injected with ST44 varied significantly (P = .0003). This dependency was also found for 3 of 5 urine parameters and 4 of 36 blood parameters (P < .05). For ST68, only 1 urine parameter showed significance (P < .0001). Giant cell infiltration in the lungs was significantly higher than controls in the ST44 0.1 mL/kg and the ST68 0.8-1.0 mL/kg groups (P < .01). It is concluded that the prudent choice for future nonrodent, toxicology studies and potentially for human clinical trials is ST68 (given the deaths in the ST44 groups).
充气体微泡可用作诊断性超声成像的造影剂。我们进行了两种表面活性剂稳定的超声造影剂（ST68 和 ST44）的临床前急性毒性研究。共有 104 只 Sprague-Dawley 大鼠（实验剂量分别为 0.1、0.2、0.8 和 1.0 mL/kg；对照组为 1.0 mL/kg 生理盐水）接受造影后 14 天的研究，评估临床症状、体重、血液和尿液。安乐死后进行组织病理学检查。在接受 ST44 治疗的 40 只动物中，有 4 只过早死亡，且表现出剂量依赖性（P =.011），而在 ST68 组中仅 1 只死亡（无剂量依赖性；P =.48）。仅注射 ST44 的大鼠体重明显变化（P =.0003）。这种依赖性也在 5 个尿液参数中的 3 个和 36 个血液参数中的 4 个中发现（P <.05）。对于 ST68，只有 1 个尿液参数有显著差异（P <.0001）。在 ST44 0.1 mL/kg 和 ST68 0.8-1.0 mL/kg 组中，肺部的巨细胞浸润明显高于对照组（P <.01）。因此，对于未来的非啮齿动物毒理学研究和潜在的人类临床试验，应谨慎选择 ST68（鉴于 ST44 组的死亡）。
