Article (Scientific journals)
Membrane type 1 matrix metalloproteinase detection in tumors, using the iodinated endogenous [123I]-tissue inhibitor 2 of metalloproteinases as imaging agent.
Van Steenkiste, Magali; Oltenfreiter, Ruth; Frankenne, Francis et al.
2010In Cancer Biotherapy and Radiopharmaceuticals, 25 (5), p. 511-20
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Keywords :
cancer; 123I; molecular imaging; MT1-MMP; TIMP-2
Abstract :
[en] 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 [(123)I]-recombinant human TIMP-2 (rhTIMP-2) as radioligand and [(123)I]-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 [(123)I]-rhTIMP-2 showed a tumor uptake of 2.87% +/- 1.58% ID/g at 3 hours postinjection in S.1.5. Tumor values of [(123)I]-rhTIMP-1 and [(123)I]-rhTIMP-2 evaluated in S.1.5 and C.IV.3, respectively, were significantly lower. Planar imaging revealed significant uptake of [(123)I]-rhTIMP-2 in S.1.5 compared with contralateral background areas. This could not be observed in C.IV.3 and with [(123)I]-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.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Van Steenkiste, Magali
Oltenfreiter, Ruth
Frankenne, Francis
Vervoort, Liesbet
Maquoi, Erik  ;  Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Noël, Agnès ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme
Foidart, Jean-Michel ;  Université de Liège - ULiège > Département des sciences cliniques > Gynécologie - Obstétrique - Labo de biologie des tumeurs et du développement
Van De Wiele, Christophe
De Vos, Filip
Language :
English
Title :
Membrane type 1 matrix metalloproteinase detection in tumors, using the iodinated endogenous [123I]-tissue inhibitor 2 of metalloproteinases as imaging agent.
Publication date :
2010
Journal title :
Cancer Biotherapy and Radiopharmaceuticals
ISSN :
1084-9785
eISSN :
1557-8852
Publisher :
Mary Ann Liebert, Inc., New Rochelle, United States - New York
Volume :
25
Issue :
5
Pages :
511-20
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 06 December 2010

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