In vivo imaging of membrane type-1 matrix metalloproteinase with a novel activatable near-infrared fluorescence probe.
Bottom Line: In aqueous buffer, MT1-hIC7L fluorescence was suppressed to background levels and increased approximately 35.5-fold in the presence of detergent.In MT1-MMP negative MCF-7 breast adenocarcinoma cells, both MT1-hIC7L and hIC7L showed no obvious fluorescence.In addition, the fluorescence intensity of C6 cells treated with MT1-hIC7L was suppressed by pre-treatment with an MT1-MMP endocytosis inhibitor (P < 0.05).
Affiliation: Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan; Central Institute of Isotope Science, Hokkaido University, Sapporo, Japan.Show MeSH
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Mentions: Compared to the hIC7L administered group, in MT1-hIC7L administered mice the fluorescence gradually increased in C6 xenografted tumors, which could be imaged clearly at 24 and 48 h post-administration (Fig. 4a). In addition, the T/B ratios of MT1-hIC7L increased with time and provided higher values than those of hIC7L (Fig. 4c, 3.2 ± 0.3 vs 2.7 ± 0.2 at 24 h, and 3.8 ± 0.3 vs 3.1 ± 0.2 at 48 h). In mice xenografted with MCF-7 cells which express low levels of MT1-MMP, there was no significant difference in the images between the MT1-hIC7L-administered and hIC7L-administered groups throughout the study duration (Fig. 4b). The T/B ratios in the MCF-7 tumors were unchanged regardless of the probe used (Fig. 4d, 2.5 ± 0.3 vs 2.6 ± 0.2 at 24 h, and 2.8 ± 0.4 vs 3.0 ± 0.2 at 48 h).
Affiliation: Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan; Central Institute of Isotope Science, Hokkaido University, Sapporo, Japan.