High sensitivity detection of cancer in vivo using a dual-controlled activation fluorescent imaging probe based on H-dimer formation and pH activation.
High sensitivity detection of cancer in vivo using a dual-controlled activation fluorescent imaging probe based on H-dimer formation and pH activation.
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DOI：
10.1039/b917876g
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发表时间：
2010-05
影响因子：
--
通讯作者：
Kobayashi H
中科院分区：
文献类型：
--
作者：
Ogawa M;Kosaka N;Regino CA;Mitsunaga M;Choyke PL;Kobayashi H
提高活体分子成像灵敏度的关键是提高靶背景信号比(TBR)。与其他分子成像方法相比，光学成像具有明显的优势，因为荧光信号可以在目标处被激活，从而减少背景信号。在此之前，我们发现H-二聚体的形成对荧光猝灭，其中TAMRA的猝灭率最高。另一种降低背景信号的方法是基于光子诱导电子转移(PET)理论的pH激活。我们假设，结合这两种策略可以产生比单独使用任何一种探针都更大的猝灭能力。将pH敏感的荧光团pHrodo或Tamra连接到肿瘤靶向分子亲和素(Av)和曲妥珠单抗(Tra)上。正如预期的那样，pHrodo和Tamra在与亲和素或抗体偶联时都形成了H-二聚体，二聚作用导致了有效的荧光猝灭。此外，PHRODO共轭探针表现出pH依赖性的荧光激活。当探针用于活体动物模型时，Av-pHrodo荧光内窥镜在注射后1小时和2小时显示高TBR的肿瘤。Av-Tamra在注射后1h和2 h也能显示肿瘤，但由于注射后1h非特异性结合的背景信号和非结合剂的背景荧光，TBR较低。因此，我们证明了基于H-二聚体形成和pH激活相结合的双重控制的可激活光学探针可以在活体分子成像的早期时间点获得高的TBR。
The key to improving the sensitivity of in vivo molecular imaging is to increase the target-to-background signal ratio (TBR). Optical imaging has a distinct advantage over other molecular imaging methods in that the fluorescent signal can be activated at the target thus reducing background signal. Previously, we found that H-dimer formation quenches fluorescence of xanthene fluorophores, and among these, TAMRA had the highest quenching ratio. Another approach to lowering background signal is to employ pH activation based on the photon-induced electron transfer (PeT) theory. We hypothesized that combining these two strategies could lead to greater quenching capacity than was possible with either probe alone. A pH-sensitive fluorophore, pHrodo or TAMRA was conjugated to the cancer targeting molecules, avidin (Av) and trastuzumab (Tra). As expected, both pHrodo and TAMRA formed H-dimers when conjugated to avidin or antibody and the dimerization resulted in efficient fluorescence quenching. In addition, pHrodo conjugated probes showed pH-dependent fluorescence activation. When the probes were used in an in vivo animal model, fluorescence endoscopy with Av-pHrodo depicted tumors with high TBR 1 h and 2 h after injection. Av-TAMRA also visualized tumors 1 h and 2 h after the injection, however, TBR was lower due to the background signal from non-specific binding 1 h after the injection as well as background fluorescence from the unbound agent. Thus, we demonstrate that a dual-controlled activatable optical probe based on the combination of H-dimer formation and pH activation can achieve high TBR at early time points during in vivo molecular imaging.
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影响因子：
5.7
作者：
Ogawa M;Regino CA;Choyke PL;Kobayashi H
通讯作者：
Kobayashi H
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
5.7
作者：
Longmire M;Kosaka N;Ogawa M;Choyke PL;Kobayashi H
通讯作者：
Kobayashi H
DOI：
10.1038/jid.2009.161
发表时间：
2009-12
期刊：
The Journal of investigative dermatology
影响因子：
--
作者：
通讯作者：
--
影响因子：
4
作者：
Ogawa, Mikako;Kosaka, Nobuyuki;Choyke, Peter L.;Kobayashi, Hisataka
通讯作者：
Kobayashi, Hisataka