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首页> 外文期刊>Anticancer Research: International Journal of Cancer Research and Treatment >Radionuclide imaging of tumor xenografts in mice using a gelatinase-targeting peptide.
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Radionuclide imaging of tumor xenografts in mice using a gelatinase-targeting peptide.

机译：使用明胶酶靶向肽对小鼠体内异种移植物进行放射性核素成像。

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摘要

Tumors express MMP-2 and MMP-9 gelatinases, which are involved in the formation of tumor vasculature. This suggests that a tumor and its surrounding neovasculature can be visualized by a sensitive gelatinase recognition method. We have studied tumor radioimaging using a gelatinase inhibitory peptide CTTHWGFTLC (CTT), which in a mouse model targets the tumor site following an intravenous injection. We determined a solution NMR structure of CTT and its retro-inversion peptide, and prepared 125I and 99mTc-labelled CTT peptide derivatives. Radiolabelled CTT inhibited gelatinases in vitro, and homed to a tumor xenograft in mice. In normal mice, CTT was instead rapidly cleared from the circulation mainly through the kidney and, after 24 h, no significant radioactivity was accumulated in healthy tissues. Gamma camera imaging of a primary tumor in live mice was obtained with double-labelled liposomes, which were coated with 99mTc-CTT and encapsulated with 125I albumin. CTT also targeted liposomes to the lungs of tumor-bearing mice, which may indicate the existence of non-visible lung micrometastases. Our studies suggest that selective gelatinase-targeting compounds could be useful in the early detection and imaging of primary tumors and metastases.
机译：肿瘤表达MMP-2和MMP-9明胶酶，它们参与肿瘤脉管系统的形成。这表明可以通过敏感的明胶酶识别方法将肿瘤及其周围的新脉管系统可视化。我们已经研究了使用明胶酶抑制肽CTTHWGFTLC（CTT）进行的肿瘤放射成像，该模型在小鼠模型中静脉注射后靶向肿瘤部位。我们确定了CTT及其逆转肽的溶液NMR结构，并制备了125I和99mTc标记的CTT肽衍生物。放射性标记的CTT在体外抑制明胶酶，并归巢于小鼠的异种移植肿瘤。在正常小鼠中，CTT主要通过肾脏从循环中迅速清除，并且在24小时后，健康组织中没有明显的放射性积累。用双标记脂质体获得了活体小鼠原发肿瘤的伽马相机成像，该脂质体涂有99mTc-CTT并包裹有125I白蛋白。 CTT还可以将脂质体靶向荷瘤小鼠的肺部，这可能表明存在不可见的肺微转移。我们的研究表明，选择性明胶酶靶向化合物可用于早期检测和成像的原发性肿瘤和转移。

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