Synthesis of Tc-99m cyclam-2-nitroimidazole: A probe for imaging tumor hypoxia

TL;DRAbstract

1606 Objectives It is known that the nitro group of 2-nitroimidazole could be reduced selectively by nitro reductase under hypoxic conditions. 1,4,8,11-tetraazabicyclohexadecane (cyclam, N4) has also shown to be a stable chelator for Tc-99m. This study was aimed to synthesize Tc-99m cyclam-2-nitroimidazole (N4-2-NIM) for tumor hypoxia imaging. Methods N4-2-NIM was synthesized by reacting N4-oxalate and 3-bromopropyl-2-NIM. After de-oxalate, N4-NIM was obtained in 14% (total synthesis). N4-AMT was labeled with Tc-99m in the presence of tin (II) chloride. In vitro cellular uptake of Tc-99m N4-2-NIM and Tc-99m N4 was conducted in 13762 rat breast tumor cells-line in 12 wells plates at 0.5-4hrs. Planar imaging was performed in breast tumor-bearing rats and VX-2 tumor bearing rabbits. Tumor and muscle oxygen tension values were measured by using an oxygen probe. Results Structure of N4-NIM was confirmed by NMR and mass spectrometry. Radiochemical purity of Tc-99m N4-2-NIM was >96% by HPLC.

Chat with Paper

AI Agents for this Paper