Radiosynthesis and evaluation of novel [99mTc(I)]+ and [99mTc(I)(CO)3]+ complexes with a 4-nitroimidazole isocyanide for imaging tumor hypoxia |
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Authors: | Qing Ruan Xuran Zhang Junbo Zhang |
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Institution: | Key Laboratory of Radiopharmaceuticals of Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, 100875 China |
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Abstract: | 99mTc(I)]+ and 99mTc(I)(CO)3]+ complexes with isocyanide exhibit high stability, which makes them suitable platforms to develop novel 99mTc radiopharmaceuticals. To develop novel 99mTc radiotracers for imaging hypoxia, in this study, a novel L ligand (4-nitroimidazole isocyanide derivative) was synthesized and labelled using 99mTc(I)]+ core and 99mTc(I)(CO)3]+ core to produce 99mTc(L)6]+ and 99mTc(CO)3(L)3]+ with high yields. To verify the structure of the 99mTc complexes, corresponding rhenium analogues were synthesized and characterized. Both of the 99mTc complexes were stable and hydrophilic. in vitro cellular uptake results showed they could exhibit good hypoxic selectivity. The evaluation of biodistribution in mice bearing S180 tumors indicated both of them could accumulate in tumor. Between them, 99mTc(L)6]+ exhibited higher tumor uptake and tumor/non-target ratio than 99mTc(CO)3(L)3]+. Further, single photon emission computed tomography (SPECT) imaging studies of 99mTc(L)6]+ indicated an obvious accumulation in tumor and the value of the region-of-interest (ROI) ratio of the uptake for the tumor site to the corresponding non-tumor region was 5.64 ± 0.52. The above results suggested 99mTc(L)6]+ would be a potential tracer for imaging tumor hypoxia. |
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Keywords: | 4-nitroimidazole 99mTc hypoxia Isocyanide tumor |
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