Radiochemistry and Radiation Chemistry Key Laboratory of Fundamental Science, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
Radiochemistry and Radiation Chemistry Key Laboratory of Fundamental Science, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
Bioorg Med Chem Lett. 2023 Feb 15;82:129154. doi: 10.1016/j.bmcl.2023.129154. Epub 2023 Jan 31.
Three nitroimidazole propylene amine oxime (PnAO) derivatives with different lengths of ethylene glycol chain were synthesized and radiolabeled with Tc. The radiochemical purities of three Tc-labeled complexes, oxo[[6,6,12,12-tetramethyl-1,17-bis(2-nitro-1H-imidazol-1-yl)-3,15-dioxa-7,11-diazaheptadecane-5, 13-dione dioximato] (3-)-N,N',N'',N''']-technetium-99m (Tc-2P2O1), oxo[[9,9,15,15-tetramethyl-1,23-bis(2-nitro-1H-imidazol-1-yl)-3,6,18,21-tetraoxa-10, 14-diazatricosane-8,16-dione dioximato] (3-)-N,N',N'',N''']-technetium-99m (Tc-2P2O2) and oxo[[15,15,21,21-tetramethyl-1,35-bis(2-nitro-1H-imidazol-1-yl)-3,6,9,12,24,27,30,33-octaoxa-16,20-diazapentatriacontane-14,22-dione dioximato] (3-)-N,N',N'',N''']-technetium-99m (Tc-2P2O4), were above 90%, and they were all stable both in vitro and in vivo. The hypoxia/normoxia uptake ratios of the three complexes were 2.92 ± 0.61, 2.63 ± 0.64 and 2.29 ± 0.67 in S180 cellular uptake assay (4 h). All of these complexes presented good hypoxia selectivity. The results of biodistribution studies in S180 tumor-bearing mice revealed that the tumor/muscle (T/M) ratios (7.20 ± 2.37, 7.19 ± 1.75, 5.56 ± 1.10) and tumor/blood (T/B) ratios (1.66 ± 0.34, 1.73 ± 0.25, 2.13 ± 0.19) at 4 h of three complexes were significantly higher than those of Tc-2P2 (3.24 ± 0.65, 0.81 ± 0.34) without the ethylene glycol chains. Among them, Tc-2P2O4 had the best T/B ratio. The new complexes have higher tumor/blood and tumor/muscle ratios by adding suitable length of ethylene glycol chain. It is helpful for the design and optimization of hypoxic imaging agents.
三种硝基咪唑丙烯胺肟（PnAO）衍生物，具有不同长度的乙二醇链，被合成并被 Tc 放射性标记。三种 Tc 标记的配合物的放射化学纯度，氧代[[6,6,12,12-四甲基-1,17-双（2-硝基-1H-咪唑-1-基）-3,15-二氧杂-7,11-二氮杂十七烷-5,13-二酮二肟ato]（3-）-N,N',N'',N''']-锝-99m（Tc-2P2O1），氧代[[9,9,15,15-四甲基-1,23-双（2-硝基-1H-咪唑-1-基）-3,6,18,21-四氧杂-10,14-二氮杂二十烷-8,16-二酮二肟ato]（3-）-N,N',N'',N''']-锝-99m（Tc-2P2O2）和氧代[[15,15,21,21-四甲基-1,35-双（2-硝基-1H-咪唑-1-基）-3,6,9,12,24,27,30,33-八氧杂-16,20-二氮杂二十五烷-14,22-二酮二肟ato]（3-）-N,N',N'',N''']-锝-99m（Tc-2P2O4）的放射化学纯度均超过 90%，且在体外和体内均稳定。在 S180 细胞摄取实验（4 h）中，三种配合物的缺氧/正常氧摄取比值分别为 2.92 ± 0.61、2.63 ± 0.64 和 2.29 ± 0.67。所有这些配合物都表现出良好的缺氧选择性。在 S180 荷瘤小鼠的生物分布研究结果表明，三种配合物在 4 h 时的肿瘤/肌肉（T/M）比值（7.20 ± 2.37、7.19 ± 1.75、5.56 ± 1.10）和肿瘤/血液（T/B）比值（1.66 ± 0.34、1.73 ± 0.25、2.13 ± 0.19）明显高于无乙二醇链的 Tc-2P2（3.24 ± 0.65、0.81 ± 0.34）。其中，Tc-2P2O4 具有最佳的 T/B 比值。通过添加合适长度的乙二醇链，新配合物具有更高的肿瘤/血液和肿瘤/肌肉比值。这有助于设计和优化缺氧成像剂。
