Hypoxia is a common phenomenon in solid tumors, and its presence inhibits the efficacy of tumor chemotherapy and radiotherapy. Accurate measurement of hypoxia before tumor treatment is essential. Three propylene amine oxime (PnAO) derivatives with different substituents attached to 2-nitroimidazole were synthesized in the work, they are 3,3,9,9-tetramethyl-1,11-bis(4-bromo-2-nitro-1-imidazol-1-yl)-4,8-diazaundecane-2,10-dione dioxime (Br2P2), 3,3,9,9-tetramethyl-1,11-bis(4-methyl-2-nitro-1-imidazol-1-yl)-4,8-diazaundecane-2,10-dione dioxime (Me2P2) and 3,3,9,9-tetramethyl-1,11-bis(4,5-dimethyl-2-nitro-1-imidazol-1-yl)-4,8-diazaundecane-2,10-dione dioxime (2Me2P2). The three compounds were radiolabeled with Tc to give three complexes([Tc]Tc-Br2P2, [Tc]Tc-Me2P2 and [Tc]Tc-2Me2P2) with good stability. [Tc]Tc-Me2P2 with a more suitable reduction potential had the highest hypoxic cellular uptake, compared with [Tc]Tc-2P2 that have been previously reported, [Tc]Tc-Br2P2 and [Tc]Tc-2Me2P2. Biodistribution results in S180 tumor-bearing mice demonstrated that [Tc]Tc-Me2P2 had the highest tumor-to-muscle (T/M) ratio (12.37 ± 1.16) at 2 h in the four complexes. Autoradiography and immunohistochemical staining results revealed that [Tc]Tc-Me2P2 specifically targeted tumor hypoxic regions. The SPECT/CT imaging results showed that [Tc]Tc-Me2P2 could target the tumor site. [Tc]Tc-Me2P2 may become a potential hypoxia imaging agent.

中文翻译：

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含有两个 4-甲基-2-硝基咪唑基团的新型 99mTc 标记的丙胺肟 (PnAO) 的制备和生物评价，作为一种有前途的肿瘤缺氧显像剂

缺氧是实体瘤中的常见现象，它的存在会抑制肿瘤化疗和放疗的疗效。肿瘤治疗前准确测量缺氧至关重要。本工作合成了三种2-硝基咪唑上带有不同取代基的丙烯胺肟（PnAO）衍生物，它们是3,3,9,9-四甲基-1,11-双(4-溴-2-硝基-1-)咪唑-1-基)-4,8-​​二氮杂十一烷-2,10-二酮二肟 (Br2P2), 3,3,9,9-四甲基-1,11-双(4-甲基-2-硝基-1-咪唑) -1-基)-4,8-​​二氮杂十一烷-2,10-二酮二肟 (Me2P2) 和 3,3,9,9-四甲基-1,11-双(4,5-二甲基-2-硝基-1-咪唑-1-基)-4,8-​​二氮杂十一烷-2,10-二酮二肟(2Me2P2)。将这三种化合物用Tc放射性标记，得到稳定性良好的三种配合物（[Tc]Tc-Br2P2、[Tc]Tc-Me2P2和[Tc]Tc-2Me2P2）。与之前报道的[Tc]Tc-2P2、[Tc]Tc-Br2P2和[Tc]Tc-2Me2P2相比，具有更合适还原电位的[Tc]Tc-Me2P2具有最高的缺氧细胞摄取。 S180荷瘤小鼠的生物分布结果表明，在四种复合物中，[Tc]Tc-Me2P2在2小时时具有最高的肿瘤与肌肉（T/M）比（12.37±1.16）。放射自显影和免疫组织化学染色结果表明，[Tc]Tc-Me2P2 特异性靶向肿瘤缺氧区域。 SPECT/CT成像结果表明[Tc]Tc-Me2P2可以靶向肿瘤部位。 [Tc]Tc-Me2P2可能成为一种潜在的缺氧显像剂。