Improving tumor/muscle and tumor/blood ratios of 99mTc-labeled nitroimidazole propylene amine oxime (PnAO) complexes with ethylene glycol linkers.
Improving tumor/muscle and tumor/blood ratios of 99mTc-labeled nitroimidazole propylene amine oxime (PnAO) complexes with ethylene glycol linkers.
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DOI：
10.1016/j.bmcl.2023.129154
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发表时间：
2023-01
影响因子：
2.7
通讯作者：
Shuo Li;Taiwei Chu
中科院分区：
文献类型：
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作者：
Shuo Li;Taiwei Chu
合成了3种不同乙二醇链长的硝基咪唑丙烯胺肟（PnAO）衍生物，并用99 mTc进行标记。~（99）mTc标记的氧代[[6，6，12，12-四甲基-1，17-双]配合物的放射化学纯度（2-硝基-1H-咪唑-1-基）-3，15-二氧杂-7，11-二氮杂十七烷-5，13-二酮二肟基]（3-）-N，N′，N′′，N′′]-锝-99 m（99 mTc-2 P2 O 1），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-10，14-二氮杂二十三烷-8，16-二酮二肟基]（3-）-N，N′，N ′′，N′]-锝-99 m（99 mTc-2 P2 O2）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-16，20-二氮杂三十五烷-14，22-二酮二肟基]（3-）-N，N′，N′′，N′′]-锝-99 m（99mTc-2P_2O_4）、（99mTc-2P_2所有配合物均表现出良好的缺氧选择性。在S180荷瘤小鼠中的生物分布研究的结果表明，肿瘤/肌肉（T/M）比（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）显著高于无乙二醇链的99 mTc-2 P2（3.24 ± 0.65，0.81 ± 0.34）。其中99 mTc-2 P2 O 4的T/B比最好。通过加入合适长度的乙二醇链，新的配合物具有更高的肿瘤/血液和肿瘤/肌肉比。为乏氧显像剂的设计和优化提供了理论依据。
Three nitroimidazole propylene amine oxime (PnAO) derivatives with different lengths of ethylene glycol chain were synthesized and radiolabeled with99mTc. The radiochemical purities of three99mTc-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 (99mTc-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 (99mTc-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 (99mTc-2P2O4), were above 90%, and they were all stable bothin vitroandin 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 of99mTc-2P2 (3.24 ± 0.65, 0.81 ± 0.34) without the ethylene glycol chains. Among them,99mTc-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.