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Membrane type 1 matrix metalloproteinase detection in tumors, using the iodinated endogenous [123I]-tissue inhibitor 2 of metalloproteinases as imaging agent

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Abstract
Matrix metalloproteinases (MMPs) are principal participants in tumor development. In addition to serve as a useful biochemical marker, MMP expression may also provide a target for the diagnostic in vivo imaging of tumors, using a radiolabeled inhibitor. This study investigates the use of membrane type 1 (MT1)-MMP as target for in vivo tumor diagnosis. Specific binding of the endogenous tissue inhibitor of metalloproteinase-2 (TIMP-2) to MT1-MMP has been previously described. In this study, biodistribution and imaging experiments were performed on MT1-MMP-overexpressing (S.1.5) and control (C.IV.3) tumor-inoculated mice using [I-123]recombinant human TIMP-2 (rhTIMP-2) as radioligand and [I-123]-rhTIMP-1 as control. The expression profile was controlled in vitro and on tumor extracts. rhTIMP-2 as well as rhTIMP-1 were labeled using the Iodogen method and characterized. Biodistribution of [I-123]-rhTIMP-2 showed a tumor uptake of 2.87% +/- 1.58% ID/g at 3 hours postinjection in S.1.5. Tumor values of [I-123]-rhTIMP-1 and [I-123]-rhTIMP-2 evaluated in S.1.5 and C.IV.3, respectively, were significantly lower. Planar imaging revealed significant uptake of [I-123]-rhTIMP-2 in S.1.5 compared with contralateral background areas. This could not be observed in C.IV.3 and with [I-123]-rhTIMP-1 in S.1.5. All tumors were well established (200-800 mg). These results suggest that rhTIMP-2 holds potential for development of radiotracers for in vivo imaging in overexpressing MT1-MMP but not in similar tumors that do not express this protease.
Keywords
INVASION, CELLS, EXPRESSION, TIMP-2, ACTIVATION, MT1-MMP, cancer, I-123, ENDOCYTOSIS, molecular imaging, THERAPEUTIC TARGET, 1-MATRIX METALLOPROTEINASE, TISSUE INHIBITOR

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Citation

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Chicago
Van Steenkiste, Magali, Ruth Oltenfreiter, Francis Frankenne, Liesbet Vervoort, Erik Maquoi, Agnes Noel, Jean-Michel Foidart, Christophe Van De Wiele, and Filip De Vos. 2010. “Membrane Type 1 Matrix Metalloproteinase Detection in Tumors, Using the Iodinated Endogenous [123I]-tissue Inhibitor 2 of Metalloproteinases as Imaging Agent.” Cancer Biotherapy and Radiopharmaceuticals 25 (5): 511–520.
APA
Van Steenkiste, M., Oltenfreiter, R., Frankenne, F., Vervoort, L., Maquoi, E., Noel, A., Foidart, J.-M., et al. (2010). Membrane type 1 matrix metalloproteinase detection in tumors, using the iodinated endogenous [123I]-tissue inhibitor 2 of metalloproteinases as imaging agent. CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS, 25(5), 511–520.
Vancouver
1.
Van Steenkiste M, Oltenfreiter R, Frankenne F, Vervoort L, Maquoi E, Noel A, et al. Membrane type 1 matrix metalloproteinase detection in tumors, using the iodinated endogenous [123I]-tissue inhibitor 2 of metalloproteinases as imaging agent. CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS. 2010;25(5):511–20.
MLA
Van Steenkiste, Magali, Ruth Oltenfreiter, Francis Frankenne, et al. “Membrane Type 1 Matrix Metalloproteinase Detection in Tumors, Using the Iodinated Endogenous [123I]-tissue Inhibitor 2 of Metalloproteinases as Imaging Agent.” CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS 25.5 (2010): 511–520. Print.
@article{1261941,
  abstract     = {Matrix metalloproteinases (MMPs) are principal participants in tumor development. In addition to serve as a useful biochemical marker, MMP expression may also provide a target for the diagnostic in vivo imaging of tumors, using a radiolabeled inhibitor. This study investigates the use of membrane type 1 (MT1)-MMP as target for in vivo tumor diagnosis. Specific binding of the endogenous tissue inhibitor of metalloproteinase-2 (TIMP-2) to MT1-MMP has been previously described. In this study, biodistribution and imaging experiments were performed on MT1-MMP-overexpressing (S.1.5) and control (C.IV.3) tumor-inoculated mice using [I-123]recombinant human TIMP-2 (rhTIMP-2) as radioligand and [I-123]-rhTIMP-1 as control. The expression profile was controlled in vitro and on tumor extracts. rhTIMP-2 as well as rhTIMP-1 were labeled using the Iodogen method and characterized. Biodistribution of [I-123]-rhTIMP-2 showed a tumor uptake of 2.87\% +/- 1.58\% ID/g at 3 hours postinjection in S.1.5. Tumor values of [I-123]-rhTIMP-1 and [I-123]-rhTIMP-2 evaluated in S.1.5 and C.IV.3, respectively, were significantly lower. Planar imaging revealed significant uptake of [I-123]-rhTIMP-2 in S.1.5 compared with contralateral background areas. This could not be observed in C.IV.3 and with [I-123]-rhTIMP-1 in S.1.5. All tumors were well established (200-800 mg). These results suggest that rhTIMP-2 holds potential for development of radiotracers for in vivo imaging in overexpressing MT1-MMP but not in similar tumors that do not express this protease.},
  author       = {Van Steenkiste, Magali and Oltenfreiter, Ruth and Frankenne, Francis and Vervoort, Liesbet and Maquoi, Erik and Noel, Agnes and Foidart, Jean-Michel and Van De Wiele, Christophe and De Vos, Filip},
  issn         = {1084-9785},
  journal      = {CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS},
  keyword      = {INVASION,CELLS,EXPRESSION,TIMP-2,ACTIVATION,MT1-MMP,cancer,I-123,ENDOCYTOSIS,molecular imaging,THERAPEUTIC TARGET,1-MATRIX METALLOPROTEINASE,TISSUE INHIBITOR},
  language     = {eng},
  number       = {5},
  pages        = {511--520},
  title        = {Membrane type 1 matrix metalloproteinase detection in tumors, using the iodinated endogenous [123I]-tissue inhibitor 2 of metalloproteinases as imaging agent},
  url          = {http://dx.doi.org/10.1089/cbr.2010.0789},
  volume       = {25},
  year         = {2010},
}

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