Sipkins D A, Cheresh D A, Kazemi M R, Nevin L M, Bednarski M D, Li K C
Lucas MRS Research Center, Department of Radiology, Stanford University School of Medicine, California 94305, USA.
Nat Med. 1998 May;4(5):623-6. doi: 10.1038/nm0598-623.
Angiogenesis, the formation of new blood vessels, is a requirement for malignant tumor growth and metastasis. In the absence of angiogenesis, local tumor expansion is suppressed at a few millimeters and cells lack routes for distant hematogenous spread. Clinical studies have demonstrated that the degree of angiogenesis is correlated with the malignant potential of several cancers, including breast cancer and malignant melanoma. Moreover, the expression of a specific angiogenesis marker, the endothelial integrin alphaVbeta3, has been shown to correlate with tumor grade. However, studies of tumor angiogenesis such as these have generally relied on invasive procedures, adequate tissue sampling and meticulous estimation of histologic microvessel density. In the present report, we describe a novel approach to detecting angiogenesis in vivo using magnetic resonance imaging (MRI) and a paramagnetic contrast agent targeted to endothelial alphaVbeta3 via the LM609 monoclonal antibody. This approach provided enhanced and detailed imaging of rabbit carcinomas by directly targeting paramagnetic agents to the angiogenic vasculature. In addition, angiogenic 'hot spots' not seen by standard MRI were detected. Our strategy for MR imaging of alphaVbeta3 thus represents a non-invasive means to assess the growth and malignant phenotype of tumors.
血管生成，即新血管的形成，是恶性肿瘤生长和转移的必要条件。在没有血管生成的情况下，局部肿瘤扩张在几毫米时就会受到抑制，并且细胞缺乏远处血行扩散的途径。临床研究表明，血管生成的程度与包括乳腺癌和恶性黑色素瘤在内的几种癌症的恶性潜能相关。此外，一种特定的血管生成标志物——内皮整合素αVβ3的表达已被证明与肿瘤分级相关。然而，诸如此类的肿瘤血管生成研究通常依赖于侵入性操作、足够的组织采样以及对组织学微血管密度的细致评估。在本报告中，我们描述了一种利用磁共振成像（MRI）和一种通过LM609单克隆抗体靶向内皮αVβ3的顺磁性造影剂在体内检测血管生成的新方法。这种方法通过将顺磁性剂直接靶向血管生成的脉管系统，提供了对兔癌的增强且详细的成像。此外，还检测到了标准MRI未发现的血管生成“热点”。因此，我们用于αVβ3磁共振成像的策略代表了一种评估肿瘤生长和恶性表型的非侵入性手段。
