Nerve-Highlighting Fluorescent Contrast Agents for Image-Guided Surgery
Nerve-Highlighting Fluorescent Contrast Agents for Image-Guided Surgery
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DOI：
10.2310/7290.2010.00026
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发表时间：
2011-03-01
影响因子：
2.8
通讯作者：
Frangioni, John V.
中科院分区：
文献类型：
--
作者：
Gibbs-Strauss, Summer L.;Nasr, Khaled A.;Frangioni, John V.
神经损伤是许多手术的主要并发症，导致慢性疼痛，功能丧失，或两者兼而有之。在外科手术过程中保留神经是一个令人烦恼的问题，因为周围的组织经常掩盖它们。迄今为止，系统给药的神经高亮对比剂可用于图像引导下的神经保护手术尚未见报道。本研究对4,4′-[（2-甲氧基-1,4-苯基）二-(1E)-2,1-乙烯二基]双苯胺（BMB）及其新合成的红移衍生物4-[(1E)-2-[4-[(1E)-2-[4-氨基苯基]乙烯基]-3-甲氧基苯基]苯腈（GE3082）的理化性质和光学性质进行了体外和体内表征。两种药物通过血神经屏障和血脑屏障，使髓鞘神经在单次全身注射后呈荧光。尽管BMB和GE3082在白色脂肪组织中也表现出明显的摄取，但GE3082在脂肪组织中发生了低色移，这为使用高光谱反卷积消除不需要的信号提供了一种手段。在小鼠身上进行了剂量和动力学研究，以确定最佳剂量和药物成像间隔。结果在大鼠和猪身上得到了证实，猪首次使用FLARE (TM)（荧光辅助切除和探查）成像系统在手术过程中同时对血管和神经进行荧光成像。这些结果为开发理想的用于图像引导手术的神经突出荧光团奠定了基础。
Nerve damage is the major morbidity of many surgeries, resulting in chronic pain, loss of function, or both. The sparing of nerves during surgical procedures is a vexing problem because surrounding tissue often obscures them. To date, systemically administered nerve-highlighting contrast agents that can be used for nerve-sparing image-guided surgery have not been reported. In the current study, physicochemical and optical properties of 4,4'-[(2-methoxy-1,4-phenylene) di-(1E)-2,1-ethenediyl] bis-benzenamine (BMB) and a newly synthesized, red-shifted derivative 4-[(1E)-2-[4-[(1E)-2-[4-aminophenyl] ethenyl]-3-methoxyphenyl] ethenyl]-benzonitrile (GE3082) were characterized in vitro and in vivo. Both agents crossed the blood-nerve barrier and blood-brain barrier and rendered myelinated nerves fluorescent after a single systemic injection. Although both BMB and GE3082 also exhibited significant uptake in white adipose tissue, GE3082 underwent a hypsochromic shift in adipose tissue that provided a means to eliminate the unwanted signal using hyperspectral deconvolution. Dose and kinetic studies were performed in mice to determine the optimal dose and drug-imaging interval. The results were confirmed in rat and pig, with the latter used to demonstrate, for the first time, simultaneous fluorescence imaging of blood vessels and nerves during surgery using the FLARE (TM) (Fluorescence-Assisted Resection and Exploration) imaging system. These results lay the foundation for the development of ideal nerve-highlighting fluorophores for image-guided surgery.