Xu Heng, Baidoo Kwamena E, Wong Karen J, Brechbiel Martin W
Radioimmune & Inorganic Chemistry Section, Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Building 10, Room 1B40, 10 Center Drive, Bethesda, MD 20892-1088, USA.
Bioorg Med Chem Lett. 2008 Apr 15;18(8):2679-83. doi: 10.1016/j.bmcl.2008.03.022. Epub 2008 Mar 10.
A novel bifunctional maleimido CHX-A'' DTPA chelator 5 was developed and conjugated to the monoclonal antibody trastuzumab (Herceptin) and subsequently radiolabeled with (111)In. The resulting (111)In labeled immunoconjugate 2 was demonstrated to bind to SKOV-3 ovarian cancer cells comparably to an isothiocyanato CHX-A'' DTPA modified native trastuzumab, 1. Through efficient thiol-maleimide chemistry, antibodies, peptides or other targeting vectors can now be modified with an established radioactive metal chelating agent CHX-A'' DTPA for imaging and/or therapies of cancer.
一种新型双功能马来酰亚胺基CHX-A'' DTPA螯合剂5被研发出来,并与单克隆抗体曲妥珠单抗(赫赛汀)偶联,随后用(111)铟进行放射性标记。结果表明,所得的(111)铟标记免疫偶联物2与异硫氰酸基CHX-A'' DTPA修饰的天然曲妥珠单抗1相比,能同等程度地结合SKOV-3卵巢癌细胞。通过高效的硫醇-马来酰亚胺化学方法,现在可以用已有的放射性金属螯合剂CHX-A'' DTPA对抗体、肽或其他靶向载体进行修饰,用于癌症的成像和/或治疗。