Microbubble Size and Dose Effects on Pharmacokinetics.
Microbubble Size and Dose Effects on Pharmacokinetics.
复制标题
微泡大小和剂量对药代动力学的影响。
DOI：
10.1021/acsbiomaterials.2c00043
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发表时间：
2022-04-11
影响因子：
5.8
通讯作者：
Borden, Mark A.
中科院分区：
文献类型：
--
作者：
Navarro-Becerra, J. Angel;Song, Kang-Ho;Martinez, Payton;Borden, Mark A.
关键词：
优化对比增强成像和聚焦超声治疗需要全面了解体内微泡药代动力学。以前的研究集中在间接技术的药代动力学分析，如血池的超声成像和呼出气体的气相色谱法。这项工作的目的是直接测量血液中的微泡浓度，并将药代动力学参数与微泡大小和剂量相关联。选择微泡体积剂量（MVD）将尺寸分布和数量联合收割机组合成单个剂量参数。以5-40 μL/kg MVD静脉注射不同尺寸的微泡（直径2、3和5 μm）。在不同时间（1-10分钟）抽取血样，并通过图像处理进行分析。当2 μm和3 μm的MVD阈值< 40 μL/kg，5 μm的MVD阈值<10 μL/kg时，微泡的清除符合一级动力学。当匹配MVD时，不同尺寸的微泡具有相当的半衰期，表明肺部的气体溶解和消除是消除的主要机制。在MVD阈值以上，微泡清除遵循双指数动力学，表明可能在肺、肝和脾中存在由器官滞留介导的第二消除机制。总之，我们提出了第一个直接的微泡药代动力学研究，证明了MVD作为一个统一的剂量度量的效用，并提供了微泡清除循环的机制的见解。
Optimization of contrast-enhanced imaging and focused ultrasound therapy requires a comprehensive understanding of in vivo microbubble pharmacokinetics. Prior studies have focused pharmacokinetic analysis on indirect techniques, such as ultrasound imaging of the blood pool and gas chromatography of exhaled gases. The goal of this work was to measure the microbubble concentration directly in blood and correlate the pharmacokinetic parameters to the microbubble size and dose. Microbubble volume dose (MVD) was chosen to combine the size distribution and number into a single dose parameter. Different microbubbles sizes (2, 3, and 5 μm diameter) at 5-40 μL/kg MVD were intravenously injected. Blood samples were withdrawn at different times (1-10 min) and analyzed by image processing. We found that an MVD threshold < 40 μL/kg for 2 and 3 μm, and <10 μL/kg for 5 μm, microbubble clearance followed first-order kinetics. When matching MVD, microbubbles of different sizes had comparable half-lives indicating that gas dissolution and elimination by the lungs are the primary mechanisms for elimination. Above the MVD threshold, microbubble clearance followed bi-exponential kinetics, suggesting a second elimination mechanism mediated by organ retention, possibly in the lung, liver and spleen. In conclusion, we present the first direct microbubble pharmacokinetic study, demonstrate the utility of MVD as a unified dose metric, and provide insights into the mechanisms of microbubble clearance from circulation.
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影响因子：
19.7
作者：
Hynynen, K;McDannold, N;Jolesz, FA
通讯作者：
Jolesz, FA
DOI：
10.1109/tbme.2009.2034533
发表时间：
2010-01
期刊：
IEEE transactions on bio-medical engineering
影响因子：
--
作者：
Choi JJ;Feshitan JA;Baseri B;Wang S;Tung YS;Borden MA;Konofagou EE
通讯作者：
Konofagou EE
影响因子：
3.9
作者：
Abenojar, Eric C.;Nittayacharn, Pinunta;Exner, Agata A.
通讯作者：
Exner, Agata A.
大鼠Spion Microbubbles的生物分布，动力学和生物命运。
影响因子：
8
作者：
Barrefelt Å;Saghafian M;Kuiper R;Ye F;Egri G;Klickermann M;Brismar TB;Aspelin P;Muhammed M;Dähne L;Hassan M
通讯作者：
Hassan M
DOI：
10.1016/0735-1097(95)00306-1
发表时间：
1995-11-01
影响因子：
24
作者：
GRAYBURN, PA;ERICKSON, JM;VELASCO, CE
通讯作者：
VELASCO, CE