Biodistribution of 99TcmO-labeled MAG3-2-nitroimidazole hypoxia imaging agents with different spacers in S180 scarcoma-bearing mice

Abstract

Objective To evaluate the hypoxia selectivity of 99TcmO-labeld MAG3-nitroimidazole complexes with different spacers. Methods Four kinds of 99TcmO-labeled MAG3-2-nitroimidazole hypoxia imaging agents with different spacers were synthesized and radiolabeled. The stability and lipid solubility of BzMAG3-2NIEA(1), BzMAG3-2NIPA(2), BzMAG3-2NIHA(3) and BzMAG3-2NIUA(4) were measured. The uptake was investigated by biodistribution experiment using S180-bearing mice. Two-sample t test was used for statistical analysis. Results All 4 99TcmO-MAG3 complexes were stable and negatively charged, showing an increasing trend in fat solubility with the increase of spacer length. In biodistribution study, tumor uptake of 99TcmO-1 and 99TcmO-2 with medium- and short-carbon chain were (0.67±0.18) and (0.65±0.18) %ID/g 2 h post injection, which were (0.19±0.03) and (0.39±0.05) %ID/g for 99TcmO-3 and 99TcmO-4 with long-carbon chain (t=2.78-5.88, all P<0.05). Conclusion Molecular structure of spacers has a significant effect on the physicochemical properties and tumor targeting of 99TcmO-labeled MAG3-2-nitroimidazole hypoxia imaging agents, such that the medium- and short-carbon chain spacers show the best hypoxia-selective property. Key words: Nitroimidazoles; Isotope labeling; Technetium; Scarcoma; Radionuclide imaging; Mice