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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.

Author information

1
Department of Radiation Oncology (MAASTRO), GROW, MUMC, Maastricht, the Netherlands.
2
Department of Toxicogenomics, GROW, MUMC, Maastricht, the Netherlands.
3
Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, ETH Zürich, Zürich, Switzerland.
4
Department of Psychology and Neuropsychology, MHeNS, MUMC, Maastricht, the Netherlands.

Abstract

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.

PMID:
26923459
PMCID:
PMC4770595
DOI:
10.1038/srep22198
[Indexed for MEDLINE]
Free PMC Article

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