Development of a Hypoxia-Selective Near-Infrared Fluorescent Probe for Non-invasive Tumor Imaging
Development of a Hypoxia-Selective Near-Infrared Fluorescent Probe for Non-invasive Tumor Imaging
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DOI：
10.1248/cpb.60.402
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发表时间：
2012-03-01
影响因子：
1.7
通讯作者：
Nagasawa, Hideko
中科院分区：
文献类型：
--
作者：
Youssif, Bahaa Gamal Mohamed;Okuda, Kensuke;Nagasawa, Hideko
设计、合成了一种近红外荧光染料CPU-311，并对其在肿瘤乏氧无创成像中的应用进行了评价。通过亲核取代和点击化学环的方法，利用含有硫醇和叠氮基团的双官能团四甘醇连接剂2与含二氯环己烯环的七甲基菁染料3偶联，得到了高效的合成方法。GPU-311具有较长的激发和发射波长(Ex/Em=785/802 nm)和较好的量子产率(0.05)。提高了GPU-311的水溶性和亲水性。在体外用GPU-311处理Suit-2/HRE-Luc胰腺癌细胞后，在低氧条件下选择性地观察到比常氧条件下更高水平的荧光。然而，给药后的小鼠异种移植模型的体内荧光成像显示，由于CPU-311通过肝脏迅速消除，其在肿瘤中的积聚不足。
A near-infrared fluorochrome, CPU-311, was designed, synthesized and evaluated for its application in non-invasive imaging of tumor hypoxia. Efficient synthesis was achieved by nucleophilic substitution and click chemistry ring using the bifunctional tetraethylene glycol linker 2 containing thiol and azide groups for the conjugation of the propargylated nitroimidazole 1 and the heptamethine cyanine dye 3 bearing a 2-chloro-1-cyclohexenyl ring. GPU-311 exhibited long excitation and emission wavelength (Ex/Em=785/802 nm) and a decent quantum yield (0.05). The water solubility and hydrophilicity of GPU-311 increased. After in vitro treatment of SUIT-2/HRE-Luc pancreatic cancer cells with GPU-311, a higher level of fluorescence was observed selectively in hypoxia than in normoxia. However, in vivo fluorescence imaging of a mouse xenograft model after GPU-311 administration revealed inadequate accumulation of CPU-311 in tumors due to its rapid elimination through the liver.