Development of 177Lu-DOTA-anti-CD20 for radioimmunotherapy
Development of 177Lu-DOTA-anti-CD20 for radioimmunotherapy
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DOI：
10.1007/s10967-010-0676-4
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发表时间：
2011
影响因子：
1.6
通讯作者：
H. Yousefnia;E. Radfar;A. Jalilian;A. Bahrami-Samani;S. Shirvani-Arani;A. Arbabi;M. Ghannadi‐Maragheh
中科院分区：
文献类型：
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作者：
H. Yousefnia;E. Radfar;A. Jalilian;A. Bahrami-Samani;S. Shirvani-Arani;A. Arbabi;M. Ghannadi‐Maragheh
利妥昔单抗依次用177lu -lutetium chloride标记。用热中子通量（4 × 1013n cm−2s−1）从天然的lu2o3样品中得到氯化lu，比活度为2.6 ~ 3 GBq/mg。以DOTA， n -羟基琥珀酰亚胺（NHS）为原料，在25℃条件下合成了大环双功能螯合剂n -琥珀酰亚胺-1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸（DOTA-NHS）。将1ml利妥昔单抗药物溶液（5mg /mL，在磷酸盐缓冲液中，pH 7.8）加入预先涂有DOTA-NHS （0.01-0.1 mg）的玻璃管中，在25℃下连续轻度搅拌15 h，获得dota -利妥昔单抗。在37℃下，24 h进行放射标记。放射薄层色谱显示，在优化条件下，总放射化学纯度为>98%（比活性= 444 MBq/mg，标记效率为82%）。最终的isotonic177Lu-DOTA-rituximab配合物通过凝胶电泳检查结构完整性控制。通过0.22 μm滤光片过滤后，Radio-TLC确保只有一种物质存在。在正常大鼠中进行了初步的生物分布研究，以确定放射免疫偶联物在168 h内的复合体分布。生物分布数据与已报道的其他antid20放射免疫偶联物一致。
Rituximab was successively labeled with177Lu-lutetium chloride.177Lu chloride was obtained by thermal neutron flux (4 × 1013n cm−2s−1) of natural Lu2O3sample with a specific activity of 2.6–3 GBq/mg. The macrocyclic bifunctional chelating agent, N-succinimidyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA-NHS) was prepared at 25 °C using DOTA, N-hydroxy succinimide (NHS) in CH2Cl2. DOTA-rituximab was obtained by the addition of 1 mL of a rituximab pharmaceutical solution (5 mg/mL, in phosphate buffer, pH 7.8) to a glass tube pre-coated with DOTA-NHS (0.01–0.1 mg) at 25 °C with continuous mild stirring for 15 h. Radiolabeling was performed at 37 °C in 24 h. Radio-thin layer chromatography showed an overall radiochemical purity of >98% at optimized conditions (specific activity = 444 MBq/mg, labeling efficacy; 82%). The final isotonic177Lu-DOTA-rituximab complex was checked by gel electrophoresis for structure integrity control. Radio-TLC was performed to ensure that only one species was present after filtration through a 0.22 μm filter. Preliminary biodistribution studies in normal rats were carried out to determine complex distribution of the radioimmunoconjugate up to 168 h. The biodistribution data were in accordance with other antiCD20 radioimmunoconjugates already reported.