Department of Medical Oncology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
Cancer Res. 2011 Jan 1;71(1):143-53. doi: 10.1158/0008-5472.CAN-10-1088. Epub 2010 Nov 17.
Non-invasive imaging of angiogenesis could ease the optimization of antiangiogenesis treatments for cancer. In this study, we evaluated the role of VEGF-PET as a biomarker of dynamic angiogenic changes in tumors following treatment with the kinase inhibitor sunitinib. The effects of sunitinib treatment and withdrawal on the tumor was investigated using the new VEGF-PET tracer (89)Zr-ranibizumab as well as (18)F-FDG PET, and (15)O-water PET in mouse xenograft models of human cancer. The obtained imaging results were compared with tumor growth, VEGF plasma levels and immunohistologic analyzes. In contrast to (18)F-FDG and (15)O-water PET, VEGF-PET demonstrated dynamic changes during sunitinib treatment within the tumor with a strong decline in signal in the tumor center and only minimal reduction in tumor rim, with a pronounced rebound after sunitinib discontinuation. VEGF-PET results corresponded with tumor growth and immunohistochemical vascular- and tumor- markers. Our findings highlight the strengths of VEGF-PET imaging to allow serial analysis of angiogenic changes in different areas within a tumor.
血管生成的无创成像可以促进抗血管生成治疗癌症的优化。在这项研究中,我们评估了 VEGF-PET 作为激酶抑制剂舒尼替尼治疗后肿瘤内动态血管生成变化的生物标志物的作用。使用新型 VEGF-PET 示踪剂(89)Zr-ranibizumab 以及(18)F-FDG PET 和(15)O-水 PET,研究了舒尼替尼治疗和停药对人肿瘤异种移植模型中肿瘤的影响。将获得的成像结果与肿瘤生长、VEGF 血浆水平和免疫组织化学分析进行了比较。与(18)F-FDG 和(15)O-水 PET 相比,VEGF-PET 在舒尼替尼治疗期间在肿瘤内显示出动态变化,肿瘤中心的信号明显下降,肿瘤边缘仅轻微减少,停药后明显反弹。VEGF-PET 结果与肿瘤生长和免疫组织化学血管和肿瘤标志物相吻合。我们的研究结果强调了 VEGF-PET 成像的优势,可用于对肿瘤内不同区域的血管生成变化进行连续分析。