Site-Specific Radioactive Labeling of Nanobodies
Site-Specific Radioactive Labeling of Nanobodies
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DOI：
10.1007/978-1-4939-8648-4_26
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发表时间：
2018-01-01
期刊：
影响因子：
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通讯作者：
Muyldermans, Serge
中科院分区：
文献类型：
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作者：
Crauwels, Maxine;Massa, Sam;Muyldermans, Serge
单结构域抗体片段，也称为纳米抗体（Nbs），越来越多地用作用于成像和/或靶向放射性核素治疗的靶向分子工具。为了将这些工具转化为临床，优选获得均匀的、明确定义的和良好表征的产品。已经表明，分选酶A，一种在金黄色葡萄球菌中发现的转肽酶，催化识别寡肽（LPXTG，称为分选标签）和寡甘氨酸功能化探针之间的位点特异性缀合。这种多功能技术设法偶联各种分子试剂，如生物素、荧光团、双功能螯合剂等，与含有sortag的靶蛋白结合。本章重点介绍双功能螯合剂的位点特异性偶联（例如，CHX-A”-DTPA）与配备有C-末端分选标签的Nb连接。与Nb偶联的螯合剂可以用In-111或Lu-177放射性标记，分别用于SPECT成像或靶向放射性核素治疗。
Single-domain antibody fragments, also called nanobodies (Nbs), are increasingly being used as targeting molecular tools for imaging and/or targeted radionuclide therapy. To translate these tools to the clinic, it is preferred to obtain a homogeneous, well-defined, and well-characterized product. It has been shown that Sortase A, a transpeptidase found in Staphylococcus aureus, catalyzes the site-specific conjugation between a recognition oligopeptide (LPXTG, known as sortag) and an oligoglycine functionalized probe. This versatile technique manages to couple various molecular reagents, such as biotin, fluorophores, bifunctional chelators, etc., to the target protein containing the sortag. This chapter focuses on the site-specific coupling of a bifunctional chelator (e.g., CHX-A"-DTPA) to a Nb equipped with a C-terminal sortag. The chelator conjugated to the Nb can be radiolabeled with In-111 or Lu-177 for SPECT imaging or targeted radionuclide therapy, respectively.