Lange Sara E S, Zheleznyak Alex, Studer Matthew, O'Shannessy Daniel J, Lapi Suzanne E, Van Tine Brian A
Division of Medical Oncology, Washington University in St. Louis, St. Louis, MO, USA.
Department of Radiology, Washington University in St. Louis, St. Louis, MO, USA.
Oncotarget. 2016 Mar 15;7(11):13082-92. doi: 10.18632/oncotarget.7552.
The complexity of sarcoma has led to the need for patient selection via in vivo biomarkers. Tumor endothelial marker-1 (TEM-1) is a cell surface marker expressed by the tumor microenvironment. Currently MORAb-004 (Ontuxizumab), an anti-TEM-1 humanized monoclonal antibody, is in sarcoma clinical trials. Development of positron emission tomography (PET) for in vivo TEM-1 expression may allow for stratification of patients, potentially enhancing clinical outcomes seen with Ontuxizumab.
Characterization of cell lines revealed clear differences in TEM-1 expression. One high expressing (RD-ES) and one low expressing (LUPI) cell line were xenografted, and mice were injected with 89Zr-Ontuxizumab. PET imaging post-injection revealed that TEM-1 was highly expressed and readily detectable in vivo only in RD-ES. In vivo biodistribution studies confirmed high radiopharmaceutical uptake in tumor relative to normal organs.
Sarcoma cell lines were characterized for TEM-1 expression. Ontuxizumab was labeled with 89Zr and evaluated for immunoreactivity preservation. 89Zr-Ontuxizumab was injected into mice with high or null expressing TEM-1 xenografts. In vivo PET imaging experiments were performed.
89Zr-Ontuxizumab can be used in vivo to determine high versus low TEM-1 expression. Reliable PET imaging of TEM-1 in sarcoma patients may allow for identification of patients that will attain the greatest benefit from anti-TEM-1 therapy.
肉瘤的复杂性使得需要通过体内生物标志物来选择患者。肿瘤内皮标志物-1（TEM-1）是一种由肿瘤微环境表达的细胞表面标志物。目前，抗TEM-1人源化单克隆抗体MORAb-004（Ontuxizumab）正在肉瘤临床试验中。开发用于体内TEM-1表达的正电子发射断层扫描（PET）可能有助于患者分层，潜在地改善使用Ontuxizumab所观察到的临床结果。
细胞系特征分析显示TEM-1表达存在明显差异。将一个高表达（RD-ES）和一个低表达（LUPI）细胞系进行异种移植，并给小鼠注射89Zr-Ontuxizumab。注射后PET成像显示，TEM-1仅在RD-ES中高表达且在体内易于检测到。体内生物分布研究证实肿瘤相对于正常器官对放射性药物的摄取较高。
对肉瘤细胞系进行TEM-1表达特征分析。用89Zr标记Ontuxizumab并评估其免疫反应性的保留情况。将89Zr-Ontuxizumab注射到TEM-1异种移植高表达或无表达的小鼠体内。进行体内PET成像实验。
89Zr-Ontuxizumab可用于体内确定TEM-1的高表达与低表达。在肉瘤患者中对TEM-1进行可靠的PET成像可能有助于识别将从抗TEM-1治疗中获得最大益处的患者。
