Sensitive β-galactosidase-targeting fluorescence probe for visualizing small peritoneal metastatic tumours in vivo.
Sensitive β-galactosidase-targeting fluorescence probe for visualizing small peritoneal metastatic tumours in vivo.
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DOI：
10.1038/ncomms7463
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发表时间：
2015-03-13
影响因子：
16.6
通讯作者：
Urano Y
中科院分区：
文献类型：
--
作者：
Asanuma D;Sakabe M;Kamiya M;Yamamoto K;Hiratake J;Ogawa M;Kosaka N;Choyke PL;Nagano T;Kobayashi H;Urano Y
肿瘤导向诊断是原位癌简便检测的最有前途的方法之一。在这里，我们集中在β-半乳糖苷酶，这是过度表达的原发性卵巢癌，作为一个分子靶点可视化腹膜转移卵巢癌。由于现有的荧光探针是不合适的，我们设计了膜可渗透的HMRef-βGal，其中优化的分子内螺环功能在激活时提供> 1，400倍的荧光增强。我们证实HMRef-βGal可灵敏地检测几种卵巢癌细胞系中的细胞内β-半乳糖苷酶活性。在体内，该探针在七种播散性人腹膜卵巢癌小鼠模型（SHIN 3、SKOV 3、OVK 18、OVCAR 3、OVCAR 4、OVCAR 5和OVCAR 8）中可视化直径小至<1 mm的转移。由于其高亮度，肉眼实时检测转移是可能的。转移的内窥镜荧光检测也被证明。结果清楚地表明，荧光引导诊断卵巢癌腹膜转移的探针的临床前潜在价值。 手术切除转移瘤仍然是卵巢癌延长生命的方法，但结节很难检测。在这里，作者表明，一种新的β-半乳糖苷酶的细胞可渗透探针可以灵敏地和特异性地检测卵巢癌小鼠模型中的腹膜转移。
Fluorescence-guided diagnostics is one of the most promising approaches for facile detection of cancer in situ. Here we focus on β-galactosidase, which is overexpressed in primary ovarian cancers, as a molecular target for visualizing peritoneal metastases from ovarian cancers. As existing fluorescence probes are unsuitable, we have designed membrane-permeable HMRef-βGal, in which the optimized intramolecular spirocyclic function affords >1,400-fold fluorescence enhancement on activation. We confirm that HMRef-βGal sensitively detects intracellular β-galactosidase activity in several ovarian cancer lines. In vivo, this probe visualizes metastases as small as <1 mm in diameter in seven mouse models of disseminated human peritoneal ovarian cancer (SHIN3, SKOV3, OVK18, OVCAR3, OVCAR4, OVCAR5 and OVCAR8). Because of its high brightness, real-time detection of metastases with the naked eye is possible. Endoscopic fluorescence detection of metastases is also demonstrated. The results clearly indicate preclinical potential value of the probe for fluorescence-guided diagnosis of peritoneal metastases from ovarian cancers. Surgical removal of the metastases remains a life-extending approach to ovarian cancer, but the nodules are difficult to detect. Here the authors show that a new cell-permeable probe for β-galactosidase can sensitively and specifically detect peritoneal metastases in mouse models of ovarian cancer.