BR38, a New Ultrasound Blood Pool Agent
BR38, a New Ultrasound Blood Pool Agent
复制标题
新型超声血池剂BR38
作者：
Michel Schneider;B. Anantharam;M. Arditi;D. Bokor;A. Broillet;P. Bussat;X. Fouillet;P. Frinking;I. Tardy;J. Terrettaz;R. Senior;F. Tranquart
目的：评价一种新型微泡血池造影剂BR 38的超声造影效果。材料和方法：用库尔特计数法测定BR 38微泡的大小特征。后向散射和衰减系数被确定为频率的函数。其他测量包括表面电荷、渗透压、粘度和耐静水压性。在大鼠和犬中对最终制剂进行了广泛的药理学和毒理学研究。在家兔中测定气体组分C4 F10的血液水平和消除。在猪中进行对比增强超声心动图检查，重点是心肌和肝脏。最后，在人类志愿者的I期临床研究中进行了安全性测试和初步成像实验。结果：BR 38混悬液是等渗的、非粘性的，并且显示出高的耐静水压性。它们的后向散射系数在≥2 MHz时很高，衰减在4 MHz时显示出最大值，在较高频率时缓慢下降。在重复毒理学研究中观察到的1 L/kg（大鼠）和5 L/kg（犬）的无不良作用水平（表示为微泡气体体积）分别相当于人类预期成像剂量（0.02 L/kg）的50倍和250倍。在大鼠和犬中未观察到对心血管和呼吸参数的影响。C4 F10在几分钟内从血液中消除，并在呼出的空气中排出。影像学实验显示心肌和肝脏强烈而持续的强化。在肝脏、动物和人类志愿者中观察到晚期。在I期人类志愿者中未观察到严重不良事件以及生命体征、心电图和实验室检查的显著变化。结论：BR 38显示出非常好的安全性。它的特点是持久性和低阴影。BR 38是一种很有前途的超声血池剂，可用于非心脏和心脏应用，包括心肌灌注成像。
Objective:To evaluate BR38, a new microbubble-based blood pool agent for contrast-enhanced ultrasound imaging. Materials and Methods:The size characteristics of BR38 microbubbles were measured by Coulter counting. The backscatter and attenuation coefficients were determined as a function of frequency. Additional measurements included the surface charge, osmolality, viscosity, and resistance to hydrostatic pressure. Extensive pharmacological and toxicological studies were conducted on the final formulation in rats and dogs. The blood levels and elimination of the gaseous component C4F10 were determined in the rabbit. Contrast-enhanced echographic examinations were performed in pigs focusing on the myocardium and the liver. Finally, safety testing and preliminary imaging experiments were performed in a Phase I clinical study in human volunteers. Results:BR38 suspensions are isotonic, nonviscous, and show a high resistance to hydrostatic pressure. Their backscatter coefficient is high at ≥2 MHz and attenuation shows a maximum at 4 MHz, slowly decreasing at higher frequencies. The no adverse effect levels of 1 &mgr;L/kg (rats) and 5 &mgr;L/kg (dogs) expressed as microbubble gas volume, observed in repeated toxicology studies, correspond to 50 and 250 times the expected imaging dose in human beings (0.02 &mgr;L/kg), respectively. No effects on cardiovascular and respiratory parameters were observed in rats and dogs. C4F10 is eliminated within minutes from blood and excreted in expired air. Imaging experiments showed strong and persistent enhancement of the myocardium and the liver. A late phase was observed in the liver, in animals and in human volunteers. No serious adverse events and no significant changes in vital signs, electrocardiographs, and laboratory tests were observed in Phase I human volunteers. Conclusions:BR38 shows a very good safety profile. It is characterized by a long persistence and low shadowing. BR38 is a promising ultrasound blood pool agent for noncardiac and cardiac applications including myocardial perfusion imaging.
影响因子：
19.7
作者：
Pysz, Marybeth A.;Foygel, Kira;Willmann, Juergen K.
通讯作者：
Willmann, Juergen K.