title: Preparation and biological evaluation of ⁹⁹mTc-N4IPA for single photon emission computerized tomography imaging of hypoxia in mouse tumor.
abstract: 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.
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.forename: Hua
authors.initials: H
authors.lastname: Zhu
authors.forename: Tai-Wei
authors.initials: TW
authors.lastname: Chu
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D006801:Humans; D000860:Hypoxia / Q000175:diagnosis*; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000175:diagnosis*; D015609:Organotechnetium Compounds / Q000008:administration & dosage / Q000737:chemistry; D013997:Time Factors; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D015609:Organotechnetium Compounds; C000589297:technetium 99m 1-(4-nitroimidazolyl)propanehydroxyiminoamide
keywords: 4-Nitroimidazoles; Hypoxia imaging; Technium-99m; Tumor