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Diagnosing Drug-Induced Liver Injury by Multispectral Optoacoustic Tomography and Fluorescence Imaging Using a Leucine-Aminopeptidase-Activated Probe.
Analytical Chemistry ( IF 6.7 ) Pub Date : 2019-05-30 00:00:00 , DOI: 10.1021/acs.analchem.9b00107 Yong Huang 1 , Yu Qi 1 , Chenyue Zhan 1 , Fang Zeng 1 , Shuizhu Wu 1
Analytical Chemistry ( IF 6.7 ) Pub Date : 2019-05-30 00:00:00 , DOI: 10.1021/acs.analchem.9b00107 Yong Huang 1 , Yu Qi 1 , Chenyue Zhan 1 , Fang Zeng 1 , Shuizhu Wu 1
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Drug-induced liver injury (DILI) is a frequent cause of hepatic dysfunction as well as the single most frequent reason for removing approved medications from the market, and multispectral optoacoustic tomography (MSOT) is an emerging and noninvasive imaging modality for diagnosing and monitoring diseases. Herein, we report an activatable optoacoustic probe for imaging DILI through detecting the activity of leucine aminopeptidase (LAP). In this probe, an N-terminal leucyl moiety serving as the LAP recognition element is linked with a chromene-benzoindolium chromophore via 4-aminobenzylalcohol group. The elevated expression of hepatic LAP as a result of DILI cleaves the leucyl moiety and causes the red-shift of the probe’s absorption band, thereby generating prominent optoacoustic signals for MSOT imaging. During this process, the probe also exhibits prominent NIR fluorescence, which can be utilized for fluorescent imaging. More importantly, by rendering stacks of cross-sectional images as maximal intensity projection (MIP) images, we could precisely locate the focus of drug-induced liver injury in mice. This probe is expected to serve a powerful tool for studying physiological and pathological processes related to LAP.
中文翻译：
通过多光谱光声层析成像和使用亮氨酸-氨基肽酶激活探针的荧光成像诊断药物诱发的肝损伤。
药物诱发性肝损伤（DILI）是导致肝功能障碍的常见原因，也是从市场上撤消已批准药物的最常见原因，而多光谱光声层析成像（MSOT）是一种新兴的非侵入性成像方式，用于诊断和监测疾病。在本文中，我们报告了一种通过检测亮氨酸氨肽酶（LAP）的活性来成像DILI的可激活光声探针。在该探针中，用作LAP识别元件的N-末端亮基部分通过4-氨基苄醇基团与色烯-苯并吲哚鎓发色团连接。由于DILI而导致的肝LAP表达升高，会切割亮氨酰部分并引起探针吸收带的红移，从而产生用于MSOT成像的显着光声信号。在此过程中，该探针还显示出显着的NIR荧光，可用于荧光成像。更重要的是，通过将一堆横截面图像渲染为最大强度投影（MIP）图像，我们可以精确定位小鼠药物性肝损伤的焦点。该探针有望为研究与LAP相关的生理和病理过程提供有力的工具。
更新日期：2019-05-30
中文翻译：
通过多光谱光声层析成像和使用亮氨酸-氨基肽酶激活探针的荧光成像诊断药物诱发的肝损伤。
药物诱发性肝损伤（DILI）是导致肝功能障碍的常见原因，也是从市场上撤消已批准药物的最常见原因，而多光谱光声层析成像（MSOT）是一种新兴的非侵入性成像方式，用于诊断和监测疾病。在本文中，我们报告了一种通过检测亮氨酸氨肽酶（LAP）的活性来成像DILI的可激活光声探针。在该探针中，用作LAP识别元件的N-末端亮基部分通过4-氨基苄醇基团与色烯-苯并吲哚鎓发色团连接。由于DILI而导致的肝LAP表达升高，会切割亮氨酰部分并引起探针吸收带的红移，从而产生用于MSOT成像的显着光声信号。在此过程中，该探针还显示出显着的NIR荧光，可用于荧光成像。更重要的是，通过将一堆横截面图像渲染为最大强度投影（MIP）图像，我们可以精确定位小鼠药物性肝损伤的焦点。该探针有望为研究与LAP相关的生理和病理过程提供有力的工具。
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