Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Mataojo 2055, 11400 Montevideo, Uruguay.
Org Biomol Chem. 2018 Jul 25;16(29):5275-5285. doi: 10.1039/c8ob01255e.
Pretargeted imaging, based on the highly reactive process between [1,2,4,5]tetrazines with trans-cyclooctene (TCO), appears as an attractive strategy to overcome disadvantages associated with traditional radioimmunoconjugates. To be successful, the radiolabeled component should react in vivo with the conjugated antibody and the non reactive excess clear fast from the organism. Herein, we explore the in vivo effects of hydrophilic linker incorporation into [1,2,4,5]tetrazine systems bearing a 6-hydrazinonicotinyl (HYNIC) moiety for technetium-99m coordination. Incorporation of a polypeptide chain containing hydrophilic aminoacids, resulted in a derivative with renal clearance. Pretargeted bevacizumab imaging was used as proof of concept.
基于[1,2,4,5]四嗪与反式环辛烯（TCO）之间的高反应性，前靶向成像似乎是克服传统放射性免疫偶联物相关缺点的一种有吸引力的策略。为了成功，放射性标记的部分应该在体内与共轭抗体反应，并且未反应的多余部分快速从生物体中清除。在此，我们研究了将含有亲水性氨基酸的多肽链引入带有 6-肼基烟酰基（HYNIC）部分的[1,2,4,5]四嗪系统中对锝-99m 配位的体内影响。亲水性氨基酸的多肽链的引入导致了具有肾清除率的衍生物。贝伐单抗的前靶向成像被用作概念验证。
