title: In vivo optical imaging of MMP2 immuno protein antibody: tumor uptake is associated with MMP2 activity.
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.
authors.affiliation: Department of Radiation Oncology (MAASTRO), GROW, MUMC, Maastricht, the Netherlands.
authors.forename: Kranthi Marella
authors.initials: KM
authors.lastname: Panth
authors.affiliation: Department of Radiation Oncology (MAASTRO), GROW, MUMC, Maastricht, the Netherlands.|Department of Toxicogenomics, GROW, MUMC, Maastricht, the Netherlands.
authors.forename: Twan
authors.initials: T
authors.lastname: van den Beucken
authors.affiliation: Department of Radiation Oncology (MAASTRO), GROW, MUMC, Maastricht, the Netherlands.
authors.forename: Rianne
authors.initials: R
authors.lastname: Biemans
authors.affiliation: Department of Radiation Oncology (MAASTRO), GROW, MUMC, Maastricht, the Netherlands.
authors.forename: Natasja G
authors.initials: NG
authors.lastname: Lieuwes
authors.affiliation: Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, ETH Zürich, Zürich, Switzerland.
authors.forename: Marcel
authors.initials: M
authors.lastname: Weber
authors.affiliation: Department of Psychology and Neuropsychology, MHeNS, MUMC, Maastricht, the Netherlands.
authors.forename: Mario
authors.initials: M
authors.lastname: Losen
authors.affiliation: Department of Radiation Oncology (MAASTRO), GROW, MUMC, Maastricht, the Netherlands.
authors.forename: Ala
authors.initials: A
authors.lastname: Yaromina
authors.affiliation: Department of Radiation Oncology (MAASTRO), GROW, MUMC, Maastricht, the Netherlands.
authors.forename: Ludwig J
authors.initials: LJ
authors.lastname: Dubois
authors.affiliation: Department of Radiation Oncology (MAASTRO), GROW, MUMC, Maastricht, the Netherlands.
authors.forename: Philippe
authors.initials: P
authors.lastname: Lambin
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004789:Enzyme Activation; D015870:Gene Expression; D064593:Heterografts; D039302:Integrin alphaVbeta3 / Q000235:genetics / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D057054:Molecular Imaging / Q000379:methods*; D009369:Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D061848:Optical Imaging / Q000379:methods*; D015203:Reproducibility of Results; D059016:Tumor Microenvironment
chemical_list: D000906:Antibodies; D039302:Integrin alphaVbeta3; D020778:Matrix Metalloproteinase 2