Real-time catheter molecular sensing of inflammation in proteolytically active atherosclerosis.
Real-time catheter molecular sensing of inflammation in proteolytically active atherosclerosis.
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蛋白水解活性动脉粥样硬化中炎症的实时导管分子传感。
DOI：
10.1161/circulationaha.108.785881
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发表时间：
2008-10-28
期刊：
影响因子：
37.8
通讯作者：
Weissleder R
中科院分区：
文献类型：
--
作者：
Jaffer FA;Vinegoni C;John MC;Aikawa E;Gold HK;Finn AV;Ntziachristos V;Libby P;Weissleder R
为了能够在动脉粥样硬化中进行炎症的血管内检测，我们开发了一种基于近红外荧光（NIRF）导管的策略，以在血管导管插入术期间感测半胱氨酸蛋白酶活性。NIRF导管基于临床冠状动脉导丝设计。在NIR荧光斑块的体模研究中，与盐水相比，血液仅产生轻微（<30%）的荧光信号衰减，这证实了NIR窗口的有利光学性质。使用动脉粥样硬化家兔（n=11）进行体内导管评价。家兔接受注射半胱氨酸蛋白酶可激活的NIRF成像剂（Prosense 750，激发/发射750/770 nm）或盐水。通过充满血液的髂动脉的导管回撤在注射探针后24小时检测到NIRF信号。在蛋白酶试剂组中，体内峰值斑块目标与背景比（TBR）比对照组大558%（平均值±SEM，6.8±1.9对1.3±0.3，p<0.05）。离体荧光反射成像证实了这些结果（TBR 10.3±1.8试剂对1.8±0.3盐水，p<0.01）。仅在蛋白酶组中，生理盐水冲洗调制的NIRF信号谱进一步区分了动脉粥样硬化和体内正常节段（p<0.01）。体内和离体斑块TBR之间存在良好的相关性（r=0.82，p<0.01）。组织学分析表明，仅蛋白酶试剂组的噬斑中有强的NIRF信号。NIRF信号与免疫反应性巨噬细胞和半胱氨酸蛋白酶组织蛋白酶B共定位。血管内荧光导管可以使用可激活的NIRF试剂实时检测人类冠状动脉大小的血管中的半胱氨酸蛋白酶活性。这种策略可以帮助检测小动脉中的炎症和高危斑块。
To enable intravascular detection of inflammation in atherosclerosis, we developed a near-infrared fluorescence (NIRF) catheter-based strategy to sense cysteine protease activity during vascular catheterization. The NIRF catheter was designed based on a clinical coronary artery guidewire. In phantom studies of NIR fluorescent plaques, blood produced only a mild (<30%) attenuation of the fluorescence signal compared to saline, affirming the favorable optical properties of the NIR window. Catheter evaluation in vivo utilized atherosclerotic rabbits (n=11). Rabbits received an injection of a cysteine protease-activatable NIRF imaging agent (Prosense750, excitation/emission 750/770 nm) or saline. Catheter pullbacks through the blood-filled iliac artery detected NIRF signals 24 hours after injection of the probe. In the protease agent group, the in vivo peak plaque target-to-background ratio (TBR) was 558% greater than controls (mean±SEM, 6.8±1.9 vs. 1.3±0.3, p<0.05). Ex vivo fluorescence reflectance imaging corroborated these results (TBR 10.3±1.8 agent vs. 1.8±0.3 saline, p<0.01). In the protease group only, saline flush-modulated NIRF signal profiles further distinguished atheromata from normal segments in vivo (p<0.01). Good correlation between the in vivo and ex vivo plaque TBR was present (r=0.82, p<0.01). Histopathological analyses demonstrated strong NIRF signal in plaques only from the protease agent group. NIRF signals colocalized with immunoreactive macrophages and the cysteine protease cathepsin B. An intravascular fluorescence catheter can detect cysteine protease activity in vessels the size of human coronary arteries in real-time using an activatable NIRF agent. This strategy could aid in detecting inflammation and high-risk plaques in small-sized arteries.