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

• 99mTc-N4IPA was synthesized and evaluated for clinical tumor hypoxia imaging.
• Cell uptake of 99mTc-N4IPA in hypoxic was about 3 time higher than in aerobic.
• 99mTc-N4IPA SPECT imaging of U87-bearing mice clearly delineated tumors.
• 99mTc-N4IPA autoradiogram in tissues of hypoxia overlaps with hypoxyprobe-1 stained.

In order to develop technetium-99m labeled nitroimidazole imaging agent for hypoxia in tumor, we have synthesized 99mTc-1-(4-nitroimidazole-yl)-propanhydroxyiminoamide, 99mTc-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 99mTc-N4IPA may have potential as clinical hypoxia imaging agent. The key features of the biological evaluation include the following: (1) the autoradiogram of 99mTc-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 99mTc-N4IPA, reaching ID% of 8.48 ± 4.51; (3) the main pathways of excretion of 99mTc-N4IPA are through kidneys and livers in both A549 or U87-bearing tumor mice.

99mTc-N4IPA was synthesized for tumor hypoxia imaging. Its cell uptake in hypoxic were about 3 times higher than in aerobic. 99mTc-N4IPA SPECT imaging of U87-bearing mice clearly identifies tumors.Figure optionsDownload as PowerPoint slide