Fluorophore-quencher based activatable targeted optical probes for detecting in vivo cancer metastases.
Fluorophore-quencher based activatable targeted optical probes for detecting in vivo cancer metastases.
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DOI：
10.1021/mp800115t
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发表时间：
2009-03
影响因子：
4.9
通讯作者：
Kobayashi H
中科院分区：
文献类型：
--
作者：
Ogawa M;Kosaka N;Longmire MR;Urano Y;Choyke PL;Kobayashi H
肿瘤的体内分子靶向荧光成像已被提出作为改善癌症检测和管理的策略。可激活的荧光团在结合肿瘤细胞后将其荧光增加10倍，导致比常规荧光团高得多的靶与背景比率。我们开发了一种基于荧光团-猝灭剂对的体内靶向可活化光学成像探针，该探针与靶向部分结合。利用该系统，荧光在癌细胞外被荧光团-猝灭剂相互作用猝灭，但在靶细胞内被荧光团-猝灭剂对的解离激活。我们选择了塔姆拉（荧光团）-QSY 7（猝灭剂）对，并将其与抗生物素蛋白（靶向d-半乳糖受体）或曲妥珠单抗（抗人上皮生长因子受体2型（HER 2/neu）的单克隆抗体）结合，并评估了它们在小鼠癌症模型中的性能。合成了两种探针，TAMRA-QSY 7缀合的亲和素（Av-TM-Q7）和曲妥珠单抗（Traz-TM-Q7）。两者都表现出优于类似的自淬灭探针。SHIN 3和NIH/3 T3/HER 2+细胞的体外荧光显微镜研究表明，Av-TM-Q7和Traz-TM-Q7产生高的细胞内荧光信号。在小鼠中使用Av-TM-Q7和Traz-TM-Q7的体内成像能够检测小肿瘤。该分子成像探针基于与靶向配体缀合的荧光团-猝灭剂对，由于其高活化率和低背景信号，成功地检测了体内肿瘤。因此，这些基于荧光团猝灭剂系统的可活化探针在临床上有望用于癌症管理的“即看即治”策略。
In vivo molecularly targeted fluorescence imaging of tumors has been proposed as a strategy for improving cancer detection and management. Activatable fluorophores, which increased their fluorescence by 10-fold after binding tumor cells, result in much higher target to background ratios than conventional fluorophores. We developed an in vivo targeted activatable optical imaging probe based on a fluorophore-quencher pair, bound to a targeting moiety. With this system, fluorescence is quenched by the fluorophore-quencher interaction outside cancer cells, but is activated within the target cells by dissociation of the fluorophore-quencher pair. We selected the TAMRA (fluorophore)-QSY7 (quencher) pair and conjugated it to either avidin (targeting the d-galactose receptor) or trastuzumab (a monoclonal antibody against the human epithelial growth factor receptor type2 (HER2/neu)) and evaluated their performance in mouse models of cancer. Two probes, TAMRA-QSY7 conjugated avidin (Av-TM-Q7) and trastuzumab (Traz-TM-Q7) were synthesized. Both demonstrated better than similar self-quenching probes. In vitro fluorescence microscopic studies of SHIN3 and NIH/3T3/HER2+ cells demonstrated that Av-TM-Q7 and Traz-TM-Q7 produced high intracellular fluorescent signal. In vivo imaging with Av-TM-Q7 and Traz-TM-Q7 in mice enabled the detection of small tumors. This molecular imaging probe, based on a fluorophore-quencher pair conjugated to a targeting ligand, successfully detected tumors in vivo due to its high activation ratio and low background signal. Thus, these activatable probes, based on the fluorophore-quencher system, hold promise clinically for “see and treat” strategies of cancer management.
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DOI：
10.1016/j.bbrc.2006.07.169
发表时间：
2006-09-29
影响因子：
3.1
作者：
Hama, Yukihiro;Urano, Yasuteru;Kobayashi, Hisataka
通讯作者：
Kobayashi, Hisataka
影响因子：
4.8
作者：
Shi, XP;Tugusheva, K;Hazuda, DJ
通讯作者：
Hazuda, DJ
影响因子：
2.2
作者：
Slovin, Susan F.
通讯作者：
Slovin, Susan F.
影响因子：
19.7
作者：
Alencar, Herlen;Funovics, Martin A.;Mahmood, Umar
通讯作者：
Mahmood, Umar
影响因子：
2.4
作者：
FORSTER, T
通讯作者：
FORSTER, T