This work reports the synthesis, radiolabeling and preliminary biodistribution results in tumor-bearing mice of Tc-99m(CO)(3)-labeled pegylated (PEG) 2-nitroimidazoles for tumor hypoxia imaging. The novel 2-nitroimidazole derivatives were successfully synthesized by conjugation of tridendate chelators to 2-nitroimidazole via PEG(3) linker. Radiolabeling was performed in high yield with [Tc-99m(CO)(3)](+) core to get cationic [Tc-99m(CO)(3)(BPA-PEG(3)-NIM)](+), neutral [Tc-99m(CO)(3)(AOPA-PEG(3)-NIM)] and anionic [Tc-99m(CO)(3)(IDA-PEG(3)-NIM)](-) respectively, all of which were hydrophilic and stable at room temperature. Biodistribution studies in tumor-bearing mice showed that Tc-99m(CO)(3)-labeled pegylated 2-nitroimidazoles accumulated in the tumor with low uptake. Tc-99m-chelate and charge had significant impact on partition coefficient, radiotracer tumor uptake and pharmacokinetic properties. The results indicate the need for synthetic modification of the parent 2-nitroimidazole derivatives and the Tc-99m-chelate with a view to improve the tumor targeting efficacy and in vivo kinetic profiles.
Wang JJ,Wang, JJ,Zheng, XB,et al. Synthesis and preliminary biological evaluation of Tc-99m(CO)(3)-labeled pegylated 2-nitroimidazoles[J]. JOURNAL OF RADIOANALYTICAL AND NUCLEAR CHEMISTRY,2014,300(3):1013-1020.
汪建军.,Wang, JJ.,Zheng, XB.,Wu, WS.,Yang, WJ.,...&刘宇.(2014).Synthesis and preliminary biological evaluation of Tc-99m(CO)(3)-labeled pegylated 2-nitroimidazoles.JOURNAL OF RADIOANALYTICAL AND NUCLEAR CHEMISTRY,300(3),1013-1020.
汪建军,et al."Synthesis and preliminary biological evaluation of Tc-99m(CO)(3)-labeled pegylated 2-nitroimidazoles".JOURNAL OF RADIOANALYTICAL AND NUCLEAR CHEMISTRY 300.3(2014):1013-1020.