A near-infrared fluorescent long-chain fatty acid toward optical imaging of cardiac metabolism in living mice
A near-infrared fluorescent long-chain fatty acid toward optical imaging of cardiac metabolism in living mice
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DOI：
10.1039/d2an00999d
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发表时间：
2022-08-24
期刊：
影响因子：
4.2
通讯作者：
Jin，Takashi
中科院分区：
文献类型：
--
作者：
Swamy，Mahadeva M. M.;Zubir，Mohamad Zarif Mohd;Jin，Takashi
无创脂肪酸(FA)代谢成像是评价心脏功能的关键。目前，单光子发射计算机断层扫描(SPECT)和正电子发射断层扫描(PET)被广泛应用于临床前和临床研究中的心脏代谢成像。虽然SPECT和PET可以实现高灵敏度的心脏代谢成像，但也存在一些缺点，如仪器成本高和放射性示踪剂合成。相比之下，使用荧光FAs的近红外(NIR)光学成像为心脏代谢的活体成像提供了一个简单而有用的平台。在这项工作中，我们合成了一种近红外荧光标记的长链脂肪酸(LCFA)，用于在体心脏代谢的实时成像。设计了一种近红外荧光标记的长循环伏安法，作为临床上广泛用于心脏病诊断的β-甲基[~(123)I]碘苯基-戊二酸的类似物。作为近红外荧光标记，我们使用了发射超过700 nm的Alexa 680荧光团。通过将Alexa680偶联到氨基BMPP(15-(4-(3-aminopropyl)phenyl)-3-methylpentadecanoic酸上，制备了近红外荧光的BMIPP类似物Alexa680-BMPP。近红外荧光成像显示Alexa680-BMPP在静脉注射后被小鼠心脏组织摄取，表明Alexa680-BMPP可以作为荧光LCFA类似物。在Alexa680结合的FA类似物中，包括短链和中链的近红外荧光FA，Alexa680-BMPP被心脏组织摄取的效率最高。通过体内和体外近红外荧光成像，可以清楚地观察到禁食和喂养的小鼠心脏组织摄取Alexa680-BMPP的程度的差异。在这里，我们介绍了近红外荧光LCFA的合成，Alexa680-BMPP，以及它对活体小鼠心脏代谢的实时光学成像能力。
Non-invasive fatty acid (FA) metabolic imaging is crucial for the evaluation of cardiac function in the heart. Currently, single-photon emission computed tomography (SPECT) and positron emission tomography (PET) are widely employed for cardiac metabolic imaging both in pre-clinical and clinical studies. Although SPECT and PET enable highly sensitive cardiac metabolic imaging, there are several disadvantages such as the high cost of instruments and radioactive tracer synthesis. In contrast, near-infrared (NIR) optical imaging using fluorescent FAs provides a simple and useful platform for in vivo imaging of cardiac metabolism. In this work, we synthesized a NIR fluorescence labelled long-chain fatty acid (LCFA) for real-time imaging of cardiac metabolism in vivo. A NIR fluorescence labelled LCFA was designed as an analogue of β-methyl [123I] iodophenyl-pentanedecanoic acid (123I-BMIPP), which is widely used for the diagnosis of heart diseases in clinical practice. As a NIR fluorescent label, we used an Alexa 680 fluorophore that emits over 700 nm. By conjugation of Alexa 680 to Amino-BMPP (15-(4-(3-aminopropyl)phenyl)-3-methylpentadecanoic acid), we prepared a NIR fluorescent BMIPP analogue, Alexa680-BMPP. NIR fluorescence imaging showed that Alexa680-BMPP is taken up by the mouse heart tissue after intravenous injection, showing that Alexa680-BMPP can act as a fluorescent LCFA analogue. Among Alexa680 conjugated FA analogues including short and middle chain NIR fluorescent FAs, Alexa680-BMPP was most efficiently taken up by heart tissues. For fasted and fed mice, the difference in the degree of the uptake of Alexa680-BMPP in their heart tissues was clearly observed by in vivo and ex vivo NIR fluorescence imaging. Herein, we present the synthesis of a NIR fluorescent LCFA, Alexa680-BMPP, and its capability for real-time optical imaging of cardiac metabolism in living mice.