Development of Tc-99m-N4-NIM for Molecular Imaging of Tumor Hypoxia

作者：Ali Mohammad S^*; Kong Fan Lin; Rollo Alex; Mendez Richard; Kohanim Saady; Smith Daniel Lee; Yang David J

来源：Journal of Biomedicine and Biotechnology, 2012, 828139.

DOI：10.1155/2012/828139

The nitro group of 2-nitroimidazole (NIM) enters the tumor cells and is bioreductively activated and fixed in the hypoxia cells. 1,4, 8,11-tetraazacyclotetradecane (N4) has shown to be a stable chelator for Tc-99m. The present study was aimed to develop Tc-99m-cyclam-2-nitroimidazole (Tc-99m-N4-NIM) for tumor hypoxia imaging. N4-NIM precursor was synthesized by reacting N4-oxalate and 1,3-dibromopropane-NIM, yielded 14% (total synthesis). Cell uptake of Tc-99m-N4-NIM and Tc-99m-N4 was obtained in 13762 rat mammary tumor cells and mesothelioma cells in 6-well plates. Tissue distribution of Tc-99m-N4-NIM was evaluated in breast-tumor-bearing rats at 0.5-4 hrs. Tumor oxygen tension was measured using an oxygen probe. Planar imaging was performed in the tumor-bearing rat and rabbit models. Radiochemical purity of Tc-99m-N4-NIM was %26gt;96% by HPLC. Cell uptake of Tc-99m-N4-NIM was higher than Tc-99m-N4 in both cell lines. Biodistribution of Tc-99m-N4-NIM showed increased tumor-to-blood and tumor-to-muscle count density ratios as a function of time. Oxygen tension in tumor tissue was 6-10 mmHg compared to 40-50 mmHg in normal muscle tissue. Planar imaging studies confirmed that the tumors could be visualized clearly with Tc-99m-N4-NIM in animal models. Efficient synthesis of N4-NIM was achieved. Tc-99m-N4-NIM is a novel hypoxic probe and may be useful in evaluating cancer therapy.

• 出版日期2012