Abstract
In this study, kethoxal bis-N4-dimethyl-thiosemicarbazone ( KTSM2 )、3,3,9,9-tetramethyl-2-nitroimidazol-4,8-diazaundecane- 2,10-dione dioxime ( PnAO-2-nitroimidazole ), and 4,9-diaza-3,3,10,10- tetramethyldodecan-2,11-dione dioxime ( Bn(AO)2 ) were synthesized and subsequently l led with 99mTc to get radioactive complexes. L ling efficiency, lipophilicity, and stability of the 99mTc l led complexes were examined by the analytical methods including solvent extraction, thin layer chromatography, and electrophoresis. Finally, the uptakes of the 99mTc l led complexes by Nfsa cells exposed under hypoxic and aerobic conditions and biological distribution in C3H/HeN mice were undertaken to assess the potential of the 99mTc complexes for hypoxia imaging.The results show that the complexes of 99mTc with KTSM2 formed at pH 4、with PnAO-2-nitroimidazole at pH 9, and with Bn(AO)2 at pH 9 were lipophilic、neutral, and stable. In addition, labeling efficiencies of these 99mTc -complexes were more than 90%. In vitro experiment, the uptakes of 99mTc-PnAO-2-nitroimidazole and 99mTc-Bn(AO)2 in hypoxic environment after 4~6 hours were 2 times more than those in aerobic environment. However, the uptake of 99mTc-KTSM2 showed no significantly difference between hypoxic and aerobic conditions. In biological distribution, the blood clearances of 99mTc-KTSM2、99mTc-PnAO-2-nitroimidazole, and 99mTc-Bn(AO)2 were very fast and % ID/g blood remained ＜ 55% at 10 min postinjection. The uptakes in liver by these 99mTc-complexes were higher than other organs, and an increasingly accumulated doses in the small intestines were observed between 10~60 min postinjection.These results indicate that these 99mTc-complexes, due to high lipophilicity, mainly excrete via hepatobiliary way. By this work, 99mTc-PnAO-2-nitroimidazole and 99mTc-Bn(AO)2 are evaluated to have potential as hypoxia imaging agents.