Synthesis, radiolabeling and in vivo biological evaluation of ~(99m)Tc-labeled MAG_3-based bisnitroimidazole complexes as tumor hypoxia markers

摘要

Hypoxia, as a common phenomenon in solid tumors, is of interest for its relationship with resistance to tumor therapies and malignant progression of tumor. The noninvasive nuclear medical imaging technique using hypoxia markers is an important method for the detection of tumor hypoxia. The aim of current study is designing tumor hypoxia markers with hypoxia selectivity and improved properties. TwoMAG_3-based bisnitroimidazole compounds were synthesized and purified by semipreparative HPLC. Both the MAG_3 derivatives were labeled with ~(99m)Tc-oxo-technetium core via stannous tartrate exchange method in high yields (> 95%). The ~(99m)Tc- MAG_3 complexes were stable at 37 °C, 4 h after preparation, and were more hydrophilic than ~(99m)Tc-MAMA complexes. As biodistribution results showed, clearances of background activity for both the complexes were fast and they were excreted mainly through the hepatobiliary tract and part of renal tract. Although tumor uptakes of ~(99m)Tc- MAG_3-B2NIL were lower than those of ~(99m)Tc-MAG_3-B4NIL, tumor-to-blood ratios of ~(99m)Tc-MAG_3-B2NIL showed an increasing trend and were better than those of ~(99m)Tc-MAG_3- B4NIL after 2 h due to their different blood clearances. Tumor-to-muscle ratios of ~(99m)Tc-MAG_3-B2NIL and ~(99m)Tc- MAG_3-B4NIL were similar. Comparing with ~(99m)Tc-MAMA complexes, ~(99m)Tc-MAG_3-B2NIL with better tumor-to-blood ratios exhibits improved feature for hypoxia imaging, though it has lower tumor uptake than ~(99m)Tc-MAMA complexes.