A New Bifunctional Chelator Enables Facile Biocoupling and Radiolabeling as the Basis for a Bioconjugation Kit

摘要

A new tridentate bifunctional chelator, N-(-2-picolyl)(-4- hydroxy)(-3-amino)benzoic acid (PHAB), was designed to efficiently coordinate the [~(99m)Tc(CO)_3]~+ core and facilitate coupling reactions to biomolecules. The chelator can be procured in the form of the corresponding benzotriazole ester (PHAB-OBT), which can be stored and used as a bioconjugation kit. PHABOBT reacts with modified carbohydrates with high selectivity and efficiency in a single step in both aqueous and organic media. As is desirable for a kit, no complicated chemical bench work is required. Glycoconjugate postlabeling resulted in neutral radiolabeled glycans with high radiochemical yields. Prelabeling approaches were assessed by successive reaction of PHAB-OBT with the [~(99m)Tc(CO)_3]~+ core and a modified galactose model. The radiolabeled galactose was obtained in 84% yield as defined by HPLC analysis. Biodistribution of the radioactive ~(99m)Tc-labeled chelator, as well as the glycoconjugates, were examined in mice. Noticeably different biodistribution patterns were observed that reflect trends in the uptake of carbohydrate analogues by various organs.