Imaging of CA IX with fluorescent labelled sulfonamides distinguishes hypoxic and (re)-oxygenated cells in a xenograft tumour model
Imaging of CA IX with fluorescent labelled sulfonamides distinguishes hypoxic and (re)-oxygenated cells in a xenograft tumour model
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DOI：
10.1016/j.radonc.2009.06.019
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发表时间：
2009-09-01
影响因子：
5.7
通讯作者：
Lambin, Philippe
中科院分区：
文献类型：
--
作者：
Dubois, Ludwig;Lieuwes, Natasja G.;Lambin, Philippe
背景和目的：碳酸酐酶(CA)IX被认为是缺氧的内源性市场。对CA IX具有高亲和力的荧光磺胺类化合物已被开发出来，并被证明只有在CA IX蛋白表达时和细胞缺氧时才能与细胞结合。本研究的目的是利用荧光成像技术研究移植瘤模型中CaI的体内结合特性。材料和方法：NMRI-nu小鼠皮下移植HT-29结直肠肿瘤，分别给予7%氧气、烟酰胺和Carbogen治疗，并与对照组动物进行比较。结果：与非磺胺类化合物相比，在勾画的道岔区可观察到特异性的CaI蓄积(P<；0.01)。给予烟酰胺和Carbogen，分别减少急性和慢性低氧，可防止CA1堆积(P<；0.05)。当呼吸7%氧气时，可观察到高出3倍的积累量(P<；0.01)。结论：我们的体内成像结果证实了先前的体外实验数据表明，结合和保留的CaI需要暴露在低氧环境中。荧光标记的磺胺类化合物为可视化缺氧反应提供了一个强大的工具。朝着临床可应用性迈出了重要的一步，表明了CAIX定向治疗患者选择的潜力。(C)2009爱思唯尔爱尔兰有限公司。保留所有权利。放射治疗与肿瘤学92(2009)423-428
Background and purpose: Carbonic anhydrase (CA) IX is suggested to be an endogenous market of hypoxia. Fluorescent sulfonamides with a high affinity for CA IX (CAI) have been developed and shown to bind to cells only when CA IX protein was expressed and while cells were hypoxic. The aim of this study was to investigate the in vivo CAI binding properties in a xenograft tumour model using fluorescent imaging.Materials and methods: NMRI-nu mice subcutaneously transplanted with HT-29 colorectal tumours were treated with 7% oxygen or with nicotinamide and carbogen and were compared with control animals. CAI accumulation was monitored by non-invasive fluorescent imaging.Results: Specific CAI accumulation could be observed in delineated turnout areas as compared with a non-sulfonamide analogue (P < 0.01). Administration of nicotinamide and carbogen, decreasing acute and chronic hypoxia, respectively, prevented CAI accumulation (P < 0.05). When treated with 7% oxygen breathing, a 3-fold higher CAI accumulation (P < 0.01) was observed. Furthermore, the bound CAI fraction was rapidly reduced upon turnout reoxygenation (P < 0.01).Conclusions: Our in vivo imaging results confirm previous in vitro data demonstrating that CAI binding and retention require exposure to hypoxia. Fluorescent labelled sulfonamides provide a powerful tool to visualize hypoxia response. An important step is made towards clinical applicability, indicating the potential of patient selection for CA IX-directed therapies. (C) 2009 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 92 (2009) 423-428