PMID- 26923459
OWN - NLM
STAT- MEDLINE
DCOM- 20161230
LR  - 20181113
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 6
DP  - 2016 Feb 29
TI  - In vivo optical imaging of MMP2 immuno protein antibody: tumor uptake is 
      associated with MMP2 activity.
PG  - 22198
LID - 10.1038/srep22198 [doi]
LID - 22198
AB  - 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.
FAU - Panth, Kranthi Marella
AU  - Panth KM
AD  - Department of Radiation Oncology (MAASTRO), GROW, MUMC, Maastricht, the 
      Netherlands.
FAU - van den Beucken, Twan
AU  - van den Beucken T
AD  - Department of Radiation Oncology (MAASTRO), GROW, MUMC, Maastricht, the 
      Netherlands.
AD  - Department of Toxicogenomics, GROW, MUMC, Maastricht, the Netherlands.
FAU - Biemans, Rianne
AU  - Biemans R
AD  - Department of Radiation Oncology (MAASTRO), GROW, MUMC, Maastricht, the 
      Netherlands.
FAU - Lieuwes, Natasja G
AU  - Lieuwes NG
AD  - Department of Radiation Oncology (MAASTRO), GROW, MUMC, Maastricht, the 
      Netherlands.
FAU - Weber, Marcel
AU  - Weber M
AD  - Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical 
      Sciences, ETH Zurich, Zurich, Switzerland.
FAU - Losen, Mario
AU  - Losen M
AD  - Department of Psychology and Neuropsychology, MHeNS, MUMC, Maastricht, the 
      Netherlands.
FAU - Yaromina, Ala
AU  - Yaromina A
AD  - Department of Radiation Oncology (MAASTRO), GROW, MUMC, Maastricht, the 
      Netherlands.
FAU - Dubois, Ludwig J
AU  - Dubois LJ
AD  - Department of Radiation Oncology (MAASTRO), GROW, MUMC, Maastricht, the 
      Netherlands.
FAU - Lambin, Philippe
AU  - Lambin P
AD  - Department of Radiation Oncology (MAASTRO), GROW, MUMC, Maastricht, the 
      Netherlands.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160229
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Antibodies)
RN  - 0 (Integrin alphaVbeta3)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
SB  - IM
MH  - Animals
MH  - *Antibodies/immunology
MH  - Cell Line, Tumor
MH  - Disease Models, Animal
MH  - Enzyme Activation
MH  - Gene Expression
MH  - Heterografts
MH  - Integrin alphaVbeta3/genetics/metabolism
MH  - Matrix Metalloproteinase 2/genetics/immunology/*metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Molecular Imaging/*methods
MH  - Neoplasms/diagnosis/genetics/*metabolism
MH  - Optical Imaging/*methods
MH  - Reproducibility of Results
MH  - Tumor Microenvironment
PMC - PMC4770595
EDAT- 2016/03/01 06:00
MHDA- 2016/12/31 06:00
PMCR- 2016/02/29
CRDT- 2016/03/01 06:00
PHST- 2015/10/22 00:00 [received]
PHST- 2016/02/09 00:00 [accepted]
PHST- 2016/03/01 06:00 [entrez]
PHST- 2016/03/01 06:00 [pubmed]
PHST- 2016/12/31 06:00 [medline]
PHST- 2016/02/29 00:00 [pmc-release]
AID - srep22198 [pii]
AID - 10.1038/srep22198 [doi]
PST - epublish
SO  - Sci Rep. 2016 Feb 29;6:22198. doi: 10.1038/srep22198.