title: Synthesis and evaluation of a novel (99m)Tc-labeled bioreductive probe for tumor hypoxia imaging.
abstract: Tumor hypoxia is closely associated with the malignant progression and/or the high metastatic ability of tumors and often induces resistance to chemo- and/or radiotherapy. Thus, the detection and evaluation of hypoxia is important for the optimization of cancer therapy. We designed a novel (99m)Tc-labeled probe for tumor hypoxia imaging that utilizes bioreductive reactions in hypoxic cells. This probe, which contains a 4-nitrobenzyl ester group, is reduced in hypoxic cells to produce a corresponding carboxylate anion that cannot penetrate cell membranes because of its hydrophilicity and negative charge; therefore, it is expected to be trapped inside hypoxic cells. Based on this unique strategy, we synthesized the Technetium-99m ((99m)Tc)-labeled probe (99m)Tc-SD32. The uptake of (99m)Tc-SD32 in tumor cells was investigated under normoxic and hypoxic conditions. (99m)Tc-SD32 showed sufficient accumulation and good retention in hypoxic cells. In addition, we demonstrated that (99m)Tc-SD32 was subjected to bioreduction in hypoxic cells and was trapped as the corresponding carboxylate anion. These results indicated that (99m)Tc-SD32 would be a promising agent for in vivo hypoxia imaging.
authors.affiliation: Functional Imaging Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, Japan.
authors.forename: Sadaaki
authors.initials: S
authors.lastname: Kimura
authors.forename: Izumi O
authors.initials: IO
authors.lastname: Umeda
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Moriyama
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Fujii
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D051379:Mice; D009369:Neoplasms / Q000175:diagnosis*; D015609:Organotechnetium Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry; D013667:Technetium / Q000737:chemistry; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D013667:Technetium