Melhus Katrine B, Larsen Roy H, Stokke Trond, Kaalhus Olav, Selbo Pål K, Dahle Jostein
Department of Radiation Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, Oslo, Norway.
Cancer Biother Radiopharm. 2007 Aug;22(4):469-79. doi: 10.1089/cbr.2007.371.
Radioimmunotherapy (RIT) with the alpha-emitter 227Th is currently under evaluation. 227Th is conjugated to the chimeric anti-CD20 monoclonal antibody rituximab, using the chelator p-isothiocyanato-benzyl-DOTA. In this study, the binding of 227Th-DOTA-p-benzyl-rituximab to three different CD-20-positive lymphoma cell lines, Raji, Rael, and Daudi, were evaluated. Equilibrium and kinetic binding experiments were used to determine binding parameters, including the association and dissociation rate constants, the equilibrium dissociation constants, and the total number of antigens for Raji, Rael, and Daudi cells. There were significant differences between the cell lines with respect to both Kd and the total number of antigens. Rael cells had more than three times as many antigens as the other two cell lines, and the functional Kd found for Rael cells was significantly higher than that found for Raji and Daudi cells. These results were confirmed using flow cytometry. Rituximab was found to be localized in patches on the cell membrane. The findings indicated that 227Th-labeled rituximab has relevant antigen-targeting properties for radioimmunotherapy.
目前正在评估使用α发射体227Th进行的放射免疫疗法（RIT）。利用螯合剂对异硫氰酸苄基-DOTA，将227Th与嵌合抗CD20单克隆抗体利妥昔单抗偶联。在本研究中，评估了227Th-DOTA-p-苄基-利妥昔单抗与三种不同的CD-20阳性淋巴瘤细胞系Raji、Rael和Daudi的结合情况。采用平衡和动力学结合实验来确定结合参数，包括Raji、Rael和Daudi细胞的缔合和解离速率常数、平衡解离常数以及抗原总数。在Kd和抗原总数方面，各细胞系之间存在显著差异。Rael细胞的抗原数量是其他两个细胞系的三倍多，并且Rael细胞的功能性Kd显著高于Raji和Daudi细胞。这些结果通过流式细胞术得到了证实。发现利妥昔单抗定位于细胞膜上的斑块中。这些发现表明，227Th标记的利妥昔单抗在放射免疫疗法中具有相关的抗原靶向特性。
