Predicting IGF-1R therapy response in bone sarcomas: immuno-SPECT imaging with radiolabeled R1507.
Predicting IGF-1R therapy response in bone sarcomas: immuno-SPECT imaging with radiolabeled R1507.
复制标题
DOI：
10.1158/1078-0432.ccr-11-1488
复制
发表时间：
2011-12-15
期刊：
影响因子：
--
通讯作者：
van der Graaf WT
中科院分区：
文献类型：
--
作者：
Fleuren ED;Versleijen-Jonkers YM;van de Luijtgaarden AC;Molkenboer-Kuenen JD;Heskamp S;Roeffen MH;van Laarhoven HW;Houghton PJ;Oyen WJ;Boerman OC;van der Graaf WT
[目的]探讨111In-R1507免疫SPECT技术是否可用于预测IGF-1R对骨肉瘤的治疗效果。BALB/c裸鼠皮下接种表达IGF-1R的人骨肉瘤移植瘤(OS-1、EW-5和EW-8)，分别对针对IGF-1R胞外区的单抗R1507表现出高、中等或无反应。对IGF-1R抑制剂无效的IGF-1R阴性肿瘤(OS-33)也进行了检测。小鼠注射~(111)In-R1507(111In-R1507)。术后第1、3、7天分别进行生物分布和免疫SPECT/CT显像研究。OS-1和EW-5异种移植小鼠，腹腔注射3天。在EW-8和OS-33异种移植小鼠中。体内分布研究表明，111In-R1507在OS-1和EW-5异种移植瘤中的特异性蓄积分别为27.5±6.5%ID/g和14.0±2.8%ID/g。最重要的是，IGF-1R阳性但无反应的EW-8移植瘤对111In-R1507的摄取(6.5±1.5%ID/g，3天P.I.)与IGF-1R阴性的OS-33肿瘤相似(5.5±0.6%ID/g，P.I.)。正常组织摄取低且非特异性。相应的免疫SPECT图像通过显示111In-R1507的同质性(OS-1)、异质性(EW-5)或非特异性(EW-8和OS-33)的肿瘤摄取，清楚地区分高、中等和无反应的肿瘤。111In-R1507免疫SPECT是显示人骨肉瘤移植瘤细胞膜IGF-1R表达和靶点可及性的良好方法，可作为预测骨肉瘤患者IGF-1R治疗(R1507)反应的独立标志物。
To investigate whether 111In-R1507 immuno-SPECT, a novel non-invasive, in vivo screening method to visualize membranous Insulin-like Growth Factor 1 Receptor (IGF-1R) expression and accessibility, can be used to predict IGF-1R treatment (R1507) responsein bone sarcomas. BALB/c nude mice were subcutaneously implanted with IGF-1R-expressing human bone sarcoma xenografts (OS-1, EW-5 and EW-8) which demonstrated high, modest or no response, respectively, to R1507, a monoclonal antibody targeting the extracellular domain of IGF-1R. An IGF-1R-negative tumor (OS-33), unresponsive to IGF-1R inhibitors, was examined as well. Mice were injected with indium-111 labeled R1507 (111In-R1507). Biodistribution and immuno-SPECT/CT imaging studies were performed 1, 3 and 7 days p.i. in mice with OS-1 and EW-5 xenografts and 3 days p.i. in mice with EW-8 and OS-33 xenografts. Biodistribution studies showed specific accumulation of 111In-R1507 in OS-1 and EW-5 xenografts (27.5±6.5%ID/g and 14.0±2.8%ID/g, 3 days p.i., respectively). Most importantly, 111In-R1507 uptake in IGF-1R-positive, but unresponsive, EW-8 xenografts (6.5±1.5%ID/g, 3 days p.i.) was similar to that of the IGF-1R-negative OS-33 tumor (5.5±0.6%ID/g, 3 days p.i.). Uptake in normal tissues was low and non-specific. Corresponding immuno-SPECT images clearly discriminated between high, modest and non-responding tumors by demonstrating a homogeneous (OS-1), heterogeneous (EW-5) or non-specific (EW-8 and OS-33)tumor uptake of 111In-R1507. 111In-R1507 immuno-SPECT is an excellent method to visualize membranous IGF-1R expression and target accessibility in vivo in human bone sarcoma xenografts and may serve as an independent marker to predict IGF-1R therapy (R1507) responsein bone sarcoma patients.