Noninvasive assessment of tumor hypoxia with 99mTc labeled metronidazole

Purpose. The assessment of tumor hypoxia by imaging modality prior to radiation therapy would provide a rational means of selecting patients for treatment with radiosensitizers or bioreductive drugs. This study aimed to develop a Tc-99m-labeled metronidazole (MN) using ethylene-dicysteine (EC) as a chelator and evaluate its potential use to image tumor hypoxia. Methods. EC was conjugated to amino analogue of MN using Sulfo-N-hydroxysuccinimide and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide-HCl as coupling agents, the yield was 55%. Tissue distribution of Tc-99m-EC-MN was determined in breast tumor-bearing rats at 0.5, 2, and 4 hrs. Planar imaging and whole-body autoradiograms were performed. The data was compared to that using Tc-99m-EC (control), [F-18]fluoromisonidazole (FMISO) and [I-131] iodomisonidazole (IMISO). Results. In vivo biodistribution of Tc-99m-EC-MN in breast tumor-bearing rats showed increased tumor-to-blood and tumor-to-muscle ratios as a function of time. Conversely, tumor-to-blood values showed time-dependent decrease with Tc-99m-EC in the same time period. Planar images and autoradiograms confirmed that the tumors could be visualized clearly with Tc-99m-EC-MN from 0.5 to 4 hrs. There was no significant difference of tumor-to-blood count ratios between Tc-99m EC-MN and [I-131]MISO at 2 and 4 hrs postinjection. From 0.5 to 4 hrs, both Tc-99m-EC-MN and [I-131]IMISO have higher tumor-to-muscle ratios compared to [(18)]FMISO. Conclusions. It is feasible to use Tc-99m-EC-MN to image tumor hypoxia.