Noninvasive visualization of the activated alphavbeta3 integrin in cancer patients by positron emission tomography and [18F]Galacto-RGD.
Noninvasive visualization of the activated alphavbeta3 integrin in cancer patients by positron emission tomography and [18F]Galacto-RGD.
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DOI：
10.1371/journal.pmed.0020070
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发表时间：
2005-03
期刊：
影响因子：
15.8
通讯作者：
Schwaiger M
中科院分区：
文献类型：
--
作者：
Haubner R;Weber WA;Beer AJ;Vabuliene E;Reim D;Sarbia M;Becker KF;Goebel M;Hein R;Wester HJ;Kessler H;Schwaiger M
整合素αvβ3在血管生成和肿瘤细胞转移中发挥重要作用，目前正被评估为新的治疗方法的靶点。目前正在研究几种无创检测αvβ3表达的技术。我们开发了[18F]Galacto-RGD，一种18F标记的糖基化αvβ3拮抗剂，可以用正电子发射断层扫描（PET）监测αvβ3的表达。本研究通过对小动物PET扫描图像的定量分析表明，肿瘤中[18F]Galacto-RGD的摄取与αv - β3的表达相关，随后通过Western blot分析确定。此外，使用A431人鳞状细胞癌模型，我们证明这种方法足够敏感，可以观察肿瘤血管系统中αvβ3的表达。最重要的是，本研究表明[18F]Galacto-RGD结合PET可以无创定量评估恶性肿瘤患者肿瘤和内皮细胞上αv - β3的表达模式。[18F]Galacto-RGD和PET的分子成像可以为计划和监测针对αvβ3整合素的抗血管生成治疗提供重要信息，并可以揭示该整合素在各种疾病转移和血管生成过程中的参与和作用。利用PET扫描可视化整合素可以显示肿瘤中的血管生成，也可用于监测抗血管生成治疗
The integrin αvβ3 plays an important role in angiogenesis and tumor cell metastasis, and is currently being evaluated as a target for new therapeutic approaches. Several techniques are being studied to enable noninvasive determination of αvβ3 expression. We developed [18F]Galacto-RGD, a 18F-labeled glycosylated αvβ3 antagonist, allowing monitoring of αvβ3 expression with positron emission tomography (PET). Here we show by quantitative analysis of images resulting from a small-animal PET scanner that uptake of [18F]Galacto-RGD in the tumor correlates with αvβ3 expression subsequently determined by Western blot analyses. Moreover, using the A431 human squamous cell carcinoma model we demonstrate that this approach is sensitive enough to visualize αvβ3 expression resulting exclusively from the tumor vasculature. Most important, this study shows, that [18F]Galacto-RGD with PET enables noninvasive quantitative assessment of the αvβ3 expression pattern on tumor and endothelial cells in patients with malignant tumors. Molecular imaging with [18F]Galacto-RGD and PET can provide important information for planning and monitoring anti-angiogenic therapies targeting the αvβ3 integrins and can reveal the involvement and role of this integrin in metastatic and angiogenic processes in various diseases. Visualising integrins with PET scanning can show angiogenesis in tumors and also be used to monitor anti-angiogenic therapy
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