Kit formulation for preparation and biological evaluation of a novel 99mTc-oxo complex with metronidazole xanthate for imaging tumor hypoxia

Introduction: Achieving an ideal Tc-99m labeled nitroimidazole hypoxia marker is still considered to be of great interest. Metronidazole xanthate (MNXT) ligand was synthesized and radiolabeled with Tc-99m-glucoheptonate (GH) to form the (TcO)-Tc-99m-MNXT complex, for the potential use as a novel probe for imaging tumor hypoxia. Methods: For labeling, (TcO)-Tc-99m-MNXT was prepared by ligand-exchange reaction with Tc-99m-GH. The radiochemical purity of the (TcO)-Tc-99m-MNXT complex was measured by thin layer chromatography (TLC) and high performance liquid chromatography (HPLC). The distribution coefficient and stability of the complex was investigated. The structure of the (TcO)-Tc-99m-MNXT complex was verified by preparation and characterization of the corresponding stable rhenium complex. The cellular uptake of the (TcO)-Tc-99m-MNXT complex was determined in murine sarcoma 5180 cell lines under hypoxic and aerobic conditions. The biodistribution and single photon emission computed tomography (SPECT) image studies of the (TcO)-Tc-99m-MNXT complex were performed in mice bearing S 180 tumor. Results: The radiochemical purity of the (TcO)-Tc-99m-MNXT complex was over 90%. It had good in vitro stability and its distribution coefficient indicated that it was a hydrophilic complex. When Tc-99m and Re complexes were coinjected in HPLC, both radioactivity (for Tc-99m complex) and UV detectors (for Re complex) showed nearly identical HPLC profiles, suggesting their structures are similar. The tumor cell experiment and the biodistribution in mice bearing S 180 tumor showed that the (TcO)-Tc-99m-MNXT complex had a good hypoxic selectivity and accumulated in the tumor with high uptake and good retention. Single photon emission computed tomography (SPE') image studies showed that the tumor detection was observable. Conclusions: (TcO)-Tc-99m-MNXT is prepared from a kit without the need for purification and shows high tumor uptake, tumor/blood and tumor/muscle ratios, suggesting that it would be a promising candidate for imaging tumor hypoxia. (C) 2015 Elsevier Inc. All rights reserved.