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Sci Rep. 2016 Feb 29;6:22198. doi: 10.1038/srep22198.

In vivo optical imaging of MMP2 immuno protein antibody: tumor uptake is associated with MMP2 activity.

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Department of Radiation Oncology (MAASTRO), GROW, MUMC, Maastricht, the Netherlands.
Department of Toxicogenomics, GROW, MUMC, Maastricht, the Netherlands.
Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, ETH Zürich, Zürich, Switzerland.
Department of Psychology and Neuropsychology, MHeNS, MUMC, Maastricht, the Netherlands.


Matrix metalloproteinase-2 (MMP2) is important in tumorigenesis, angiogenesis and tumor invasion. In this study, we investigated if the Cy5-tagged small immuno protein targeting the catalytic domain of human MMP2 (aMMP2-SIP) detects MMP2 in tumors non-invasively. For this purpose, we generated MMP2 expressing (empty vector EV) and knock-down (KD) HT1080, U373 and U87 cells, which were injected subcutaneously in the lateral flank of NMRI-nu mice. Optical imaging (Optix MX2) performed at 0.5, 2, 4, 8, 24 and 48 hour post injection (h.p.i.) of Cy5 tagged aMMP2-SIP, indicated significantly lower tumor to background ratios at both 24 (P = 0.0090) and 48 h.p.i. (P < 0.0001) for the U87 MMP2-KD compared to control tumors. No differences were found for HT1080 and U373 models. U87 MMP2-KD tumors had significantly lower MMP2 activity (P < 0.0001) than EV tumors as determined by gelatin zymography in tumor sections and lysates, while no differences were observed between EV and MMP2-KD in HT1080 and U373. In line with these data, only U87 MMP2-KD tumors had a reduced tumor growth compared to control tumors (P = 0.0053). aMMP2-SIP uptake correlates with MMP2 activity and might therefore be a potential non-invasive imaging biomarker for the evaluation of MMP2 activity in tumors.

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