Synthesis, radiolabeling and in vivo biological evaluation of 99mTc-labeled MAG3-based bisnitroimidazole complexes as tumor hypoxia markers

Abstract

Abstract 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. Two MAG3-based bisnitroimidazole compounds were synthesized and purified by semi-preparative HPLC. Both the MAG3 derivatives were labeled with 99mTc-oxo-technetium core via stannous tartrate exchange method in high yields (> 95%). The 99mTc-MAG3 complexes were stable at 37 ℃, 4 h after preparation, and were more hydrophilic than 99mTc-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 99mTc-MAG3-B2NIL were lower than those of 99mTc-MAG3-B4NIL, tumor-to-blood ratios of 99mTc-MAG3-B2NIL showed an increasing trend and were better than those of 99mTc-MAG3-B4NIL after 2 h due to their different blood clearances. Tumor-to-muscle ratios of 99mTc-MAG3-B2NIL and 99mTc-MAG3-B4NIL were similar. Comparing with 99mTc-MAMA complexes, 99mTc-MAG3-B2NIL with better tumor-to-blood ratios exhibits improved feature for hypoxia imaging, though it has lower tumor uptake than 99mTc-MAMA complexes.