Microwave gallium-68 radiochemistry for kinetically stable bis(thiosemicarbazone) complexes: structural investigations and cellular uptake under hypoxia.
Microwave gallium-68 radiochemistry for kinetically stable bis(thiosemicarbazone) complexes: structural investigations and cellular uptake under hypoxia.
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DOI：
10.1039/c5dt02537k
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发表时间：
2016-01-07
期刊：
影响因子：
--
通讯作者：
Pascu SI
中科院分区：
文献类型：
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作者：
Alam IS;Arrowsmith RL;Cortezon-Tamarit F;Twyman F;Kociok-Köhn G;Botchway SW;Dilworth JR;Carroll L;Aboagye EO;Pascu SI
研究了微波加热合成的新型镓-68双缩氨基硫脲的低氧选择性。我们报道了几种双缩氨基硫脲的微波合成和快速掺入镓-68得到相应的金属配合物。在“冷”和“热”生物测试下，这些细胞被证明是稳定的，并在常氧和低氧条件下用激光扫描共聚焦显微镜、流式细胞仪和放射性细胞滞留研究进行了研究。缺氧30min后，~(68)Ga络合物滞留率比常氧细胞高34%，120min时进一步增加到53%。我们的数据表明，这类镓配合物具有适合在活细胞中成像的低氧选择性，在裸鼠体内的microPET测试表明，它们在给药后1小时内就被排泄了出去。
Hypoxia selectivity of new gallium-68 bis-(thiosemicarbazones) synthesised via microwave heating were investigated. We report the microwave synthesis of several bis(thiosemicarbazones) and the rapid gallium-68 incorporation to give the corresponding metal complexes. These proved kinetically stable under ‘cold’ and ‘hot’ biological assays and were investigated using laser scanning confocal microscopy, flow cytometry and radioactive cell retention studies under normoxia and hypoxia. 68Ga complex retention was found to be 34% higher in hypoxic cells than in normoxic cells over 30 min, further increasing to 53% at 120 min. Our data suggests that this class of gallium complexes show hypoxia selectivity suitable for imaging in living cells and in vivo tests by microPET in nude athymic mice showed that they are excreted within 1 h of their administration.