Preparation and biological evaluation of ⁹⁹mTc-N4IPA for single photon emission computerized tomography imaging of hypoxia in mouse tumor.

In order to develop technetium-99m labeled nitroimidazole imaging agent for hypoxia in tumor, we have synthesized (99m)Tc-1-(4-nitroimidazole-yl)-propanhydroxyiminoamide, (99m)Tc-N4IPA complex, in high radiochemical purity and radiochemical yield. The biological evaluation of this complex includes the in vitro/vivo stability, cell uptake and Single Photon Emission Computerized Tomography (SPECT) imaging in mouse tumor models, respectively. These results demonstrate that (99m)Tc-N4IPA may have potential as clinical hypoxia imaging agent. The key features of the biological evaluation include the following: (1) the autoradiogram of (99m)Tc-N4IPA complex in tissue samples of hypoxia overlaps with the area stained by hypoxyprobe-1; (2) SPECT imaging of U87-bearing mice clearly identifies tumors 4 h post injection of (99m)Tc-N4IPA, reaching ID% of 8.48 ± 4.51; (3) the main pathways of excretion of (99m)Tc-N4IPA are through kidneys and livers in both A549 or U87-bearing tumor mice.