Immunomedics Inc., 300 American Road, Morris Plains, New Jersey 07950, USA.
Bioconjug Chem. 2011 Sep 21;22(9):1793-803. doi: 10.1021/bc200175c. Epub 2011 Aug 9.
The coordination chemistry of a new pentadentate bifunctional chelator (BFC), NODA-MPAA 1, containing the 1,4,7-triazacyclononane-1,4-diacetate (NODA) motif with a methylphenylacetic acid (MPAA) backbone, and its ability to form stable Al(18)F chelates were investigated. The organofluoroaluminates were easily accessible from the reaction of 1 and AlF(3). X-ray diffraction studies revealed aluminum at the center of a slightly distorted octahedron, with fluorine occupying one of the axial positions. The tert-butyl protected prochelator 7, which can be synthesized in one step, is useful for coupling to biomolecules on solid phase or in solution. High yield (55-89%) aqueous (18)F-labeling was achieved in 10-15 min with a tumor-targeting peptide 4 covalently linked to 1. Defluorination was not observed for at least 4 h in human serum at 37 °C. These results demonstrate the facile application of Al(18)F chelation using BFC 1 as a versatile labeling method for radiofluorinating other heat-stable peptides for positron emission imaging.
研究了一种新的五齿双功能螯合剂（BFC）NODA-MPAA1 的配位化学，该螯合剂含有 1,4,7-三氮杂环壬烷-1,4-二乙酸（NODA）基序和甲基苯乙酸（MPAA）骨架，以及其形成稳定 Al(18)F 螯合物的能力。通过 1 和 AlF(3)的反应，很容易得到有机氟铝酸盐。X 射线衍射研究表明，铝位于略微扭曲的八面体的中心，氟占据一个轴向位置。叔丁基保护的前螯合剂 7 可以一步合成，可用于固相或溶液中与生物分子偶联。通过将肿瘤靶向肽 4 共价连接到 1 上，在 10-15 分钟内以高收率（55-89%）在水性介质中（18）F 标记。在 37°C 的人血清中，至少 4 小时内未观察到脱氟。这些结果表明，使用 BFC 1 进行 Al(18)F 螯合是一种简便的方法，可用于放射性标记其他耐热肽，用于正电子发射成像。
