EFFECT OF SURFACE ARCHITECTURE ON IN VIVO ULTRASOUND CONTRAST PERSISTENCE OF TARGETED SIZE-SELECTED MICROBUBBLES
EFFECT OF SURFACE ARCHITECTURE ON IN VIVO ULTRASOUND CONTRAST PERSISTENCE OF TARGETED SIZE-SELECTED MICROBUBBLES
复制标题
DOI：
10.1016/j.ultrasmedbio.2011.12.007
复制
发表时间：
2012-03-01
影响因子：
2.9
通讯作者：
Borden, Mark A.
中科院分区：
文献类型：
--
作者：
Chen, Cherry C.;Sirsi, Shashank R.;Borden, Mark A.
超声分子成像是一种强大的诊断手段，使用覆盖有内皮细胞生物标记物特异性靶向配体的微泡。配基对比剂的循环持久性是其对比度增强和靶向能力的关键决定因素。先前的研究表明，使用传统的暴露配体结构(ELA)将配体附着在外壳上的靶向微泡可能会引发不希望看到的配体诱导的补体激活，并减少循环时间。然而，具有埋藏配体结构(BLA)的微泡被发现抑制补体激活和延长循环时间。在本研究中，我们使用后标记技术将隐形BLA微泡设计扩展到以环状RGD多肽为靶标的大小选择(直径4至5微米)微泡。使用Visualsonics Vevo 770扫描仪在40 MHz的基本模式下测量健康小鼠肾脏的微泡循环持久性。靶向BLA微泡的循环持续时间明显长于ELA对应微泡，与非配体对照相似。使用BLA而不是ELA使循环半衰期增加了近两倍。用两室药代动力学模型分析时间强度和时间波动曲线表明，任何组的非特异性血管粘连程度都很低。这些结果证明了表面结构在超声分子成像靶向微泡设计中的重要性。(电子邮件：mark.borden@Colorado.edu)(C)2012年世界医学和生物学超声联合会。
Ultrasound molecular imaging is a powerful diagnostic modality using microbubbles coated with targeting ligands specific for endothelial biomarkers. The circulation persistence of ligand-bearing contrast agents is a key determinant in their contrast enhancement and targeting capability. Prior studies have shown that targeted microbubbles with ligands attached to the shell using the conventional exposed-ligand architecture (ELA) could trigger undesired ligand-induced complement activation and decreased circulation time. Microbubbles with the buried-ligand architecture (BLA), however, were found to inhibit complement activation and prolong circulation time. In the present study, we extended the stealth BLA microbubble design to size-selected (4 to 5-mu m diameter) microbubbles targeted with cyclic RGD peptide using the postlabeling technique. Microbubble circulation persistence was measured in the healthy mouse kidney using a Visualsonics Vevo 770 scanner operating at 40 MHz in fundamental mode. The circulation persistence for targeted BLA microbubbles was significantly longer compared with their ELA counterparts and similar to no-ligand controls. Use of the BLA instead of the ELA increased the circulation half-life approximately two-fold. Analysis of the time-intensity and time-fluctuation curves with a two-compartment pharmacokinetic model showed a minimal degree of nonspecific vascular adhesion for any group. These results demonstrate the importance of surface architecture in the design of targeted microbubbles for ultrasound molecular imaging. (E-mail: mark.borden@colorado.edu) (C) 2012 World Federation for Ultrasound in Medicine & Biology.