Imaging of tumour neovasculature by targeting the TGF-β binding receptor endoglin
Imaging of tumour neovasculature by targeting the TGF-β binding receptor endoglin
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DOI：
10.1016/s0959-8049(99)00335-4
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发表时间：
2000-03-01
影响因子：
8.4
通讯作者：
Weissleder, R
中科院分区：
文献类型：
--
作者：
Bredow, S;Lewin, M;Weissleder, R
完整肿瘤新生血管内皮细胞标记物的体内成像将在临床试验中应用于评估抗血管生成药物的疗效。虽然已经描述了各种不同的内皮标记物，但很少有人被评估为成像标记物。转化生长因子-β(转化生长因子-β)结合受体endoglin是一种增殖相关的内皮标记物。我们假设endoglin将是一个理想的成像靶点，因为它在肿瘤新生血管的增殖内皮细胞中强烈上调。我们使用了放射性标记的抗endoglin单抗，并将其新生血管结合、蓄积和体内行为与同型匹配的对照免疫球蛋白(2a)进行了比较。我们的数据显示，该探针在体内几分钟内就能特异而快速地结合，相关的放射自显影和免疫组织学支持体内的成像结果。大量表达的内皮靶点的成像绕过了通常与其他肿瘤靶向策略相关的传递障碍，并可能被用于定量分子血管生成标记物。(C)2000爱思唯尔科学有限公司。保留所有权利。
In vivo imaging of endothelial markers in intact tumour neovasculature would have applications in assessing the efficacy of antiangiogenic agents in clinical trials. Although a variety of different endothelial markers have been described, few have been evaluated as imaging markers. The transforming growth factor-beta (TGF-beta) binding receptor endoglin is a proliferation-associated endothelial marker. We hypothesised that endoglin would be an ideal target for imaging since it is strongly upregulated in proliferating endothelial cells of the tumour neovasculature. We used a radiolabelled monoclonal anti-endoglin antibody and compared its neovascular binding, accumulation and in vivo behaviour to an isotype-matched control IgG(2a). Our data show that the probe binds specifically and rapidly within minutes in vivo and that correlative autoradiography and immunohistology support the in vivo imaging findings. Imaging of abundantly expressed endothelial targets circumvents delivery barriers normally associated with other tumour targeting strategies, and can potentially be used to quantitate molecular angiogenic markers. (C) 2000 Elsevier Science Ltd. All rights reserved.