Department of Neurosurgery, Klinikum Grosshadern, Ludwig-Maximilians-Universität München, Munich, Germany.
Neuro Oncol. 2009 Dec;11(6):861-70. doi: 10.1215/15228517-2009-024.
Inhibitors targeting the integrin alpha(v)beta(3) are promising new agents currently tested in clinical trials for supplemental therapy of glioblastoma multiforme (GBM). The aim of our study was to evaluate (18)F-labeled glycosylated Arg-Gly-Asp peptide ([(18)F]Galacto-RGD) PET for noninvasive imaging of alpha(v)beta(3) expression in patients with GBM, suggesting eligibility for this kind of additional treatment. Patients with suspected or recurrent GBM were examined with [(18)F]Galacto-RGD PET. Standardized uptake values (SUVs) of tumor hotspots, galea, and blood pool were derived by region-of-interest analysis. [(18)F]Galacto-RGD PET images were fused with cranial MR images for image-guided surgery. Tumor samples taken from areas with intense tracer accumulation in the [(18)F]Galacto-RGD PET images and were analyzed histologically and immunohistochemically for alpha(v)beta(3) integrin expression. While normal brain tissue did not show significant tracer accumulation (mean SUV, 0.09 +/- 0.04), GBMs demonstrated significant but heterogeneous tracer uptake, with a maximum in the highly proliferating and infiltrating areas of tumors (mean SUV, 1.6 +/- 0.5). Immunohistochemical staining was prominent in tumor microvessels as well as glial tumor cells. In areas of highly proliferating glial tumor cells, tracer uptake (SUVs) in the [(18)F]Galacto-RGD PET images correlated with immunohistochemical alpha(v)beta(3) integrin expression of corresponding tumor samples. These data suggest that [(18)F] Galacto-RGD PET successfully identifies alpha(v)beta(3) expression in patients with GBM and might be a promising tool for planning and monitoring individualized cancer therapies targeting this integrin.
靶向整合素 α(v)β(3)的抑制剂是目前临床试验中用于胶质母细胞瘤（GBM）辅助治疗的有前途的新型药物。我们的研究目的是评估（18）F 标记的糖基化 Arg-Gly-Asp 肽（（18）F-Galacto-RGD）PET 用于非侵入性成像 GBM 患者的 α(v)β(3)表达，提示其适合这种额外治疗。疑似或复发性 GBM 患者接受（18）F-Galacto-RGD PET 检查。通过感兴趣区分析得出肿瘤热点、头皮和血池的标准化摄取值（SUV）。（18）F-Galacto-RGD PET 图像与颅脑 MRI 图像融合，用于图像引导手术。从（18）F-Galacto-RGD PET 图像中摄取强烈示踪剂的肿瘤样本进行组织学和免疫组织化学分析，以评估 α(v)β(3)整合素表达。虽然正常脑组织没有明显的示踪剂积累（平均 SUV，0.09 +/- 0.04），但 GBM 显示出明显但不均匀的示踪剂摄取，在肿瘤高度增殖和浸润的区域达到最大值（平均 SUV，1.6 +/- 0.5）。免疫组织化学染色在肿瘤微血管和神经胶质肿瘤细胞中均很明显。在高度增殖的神经胶质肿瘤细胞区域，（18）F-Galacto-RGD PET 图像中的示踪剂摄取（SUV）与相应肿瘤样本的免疫组织化学 α(v)β(3)整合素表达相关。这些数据表明，（18）F-Galacto-RGD PET 成功地鉴定了 GBM 患者的 α(v)β(3)表达，并且可能是针对这种整合素的个体化癌症治疗计划和监测的有前途的工具。
