177Lu标记单克隆抗体Rituximab

以CHX-A''''-DTPA和p-SCN-Bz-DTPA为双功能螯合剂，分别对Rituximab进行偶联，用¹⁷⁷Lu进行标记，制备¹⁷⁷Lu-Rituximab。在优化条件下，¹⁷⁷Lu对单抗偶联物CHX-A''''-DTPA-Rituximab和p-SCN-Bz-DTPA-Rituximab的标记率和放化纯度均大于99%。室温及37 ℃条件下，¹⁷⁷Lu-Rituximab在各种测试体系中均显示良好的体外稳定性。在正常小鼠体内的生物分布结果显示，¹⁷⁷Lu-Rituximab发生了分解，游离的¹⁷⁷Lu在骨中形成较高浓集。¹⁷⁷Lu-p-SCN-Bz-DTPA-Rituximab比¹⁷⁷Lu-CHX-A''''-DTPA-Rituximab的体内清除快，而且游离¹⁷⁷Lu的骨摄取低，结果表明，p-SCN-Bz-DTPA更适于作为双功能螯合剂用于单抗的¹⁷⁷Lu 标记。

Preparation and Preliminary Biological Evaluation of 177Lu Labelled Rituximab

For evaluating whether ¹⁷⁷Lu-Rituximab could be applied for radioimmunoimaging and radioimmunotherrapy of non-Hodgkin’s Lymphoma， Rituximab, a specific chimeric monoclonal antibody used in CD20-positive B-cell Non-Hodgkin’s Lymphoma, was conjugated to bifunctional chelating agents (CHX-A''''-DTPA and p-SCN-Bz-DTPA) and radiolabelled with ¹⁷⁷Lu successively. ¹⁷⁷Lu-CHX-A''''-DTPA-Rituximab and ¹⁷⁷Lu-p-SCN-Bz-DTPA-Rituximab were obtained with labelling yield and radiochemical purity higher than 99% at optimized conditions, and showed good in vitro stability in different testing system at room temperature and 37 ℃. However, the results of biodistribution in normal mice showed high uptakes in bone which indicated that ¹⁷⁷Lu released from the radiolabelled antibodies. The retention of free ¹⁷⁷Lu in the bone was lower for ¹⁷⁷Lu-p-SCN-Bz-DTPA-Rituximab compared with ¹⁷⁷Lu-CHX-A''''-DTPA-Rituximab. Our preliminary work demonstrated that p-SCN-Bz-DTPA may be more suitable for ¹⁷⁷Lu labelling of monoclonal antibodies.