Membrane type 1 matrix metalloproteinase detection in tumors, using the iodinated endogenous [123I]-tissue inhibitor 2 of metalloproteinases as imaging agent.
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.
Van Steenkiste
Magali
M
Laboratory of Radiopharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium. magali.vansteenkiste@skynet.be
Oltenfreiter
Ruth
R
Frankenne
Francis
F
Vervoort
Liesbet
L
Maquoi
Erik
E
Noel
Agnes
A
Foidart
Jean-Michel
JM
Van De Wiele
Christophe
C
De Vos
Filip
F
D000818:Animals; D045744:Cell Line, Tumor; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000032:analysis* / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D057054:Molecular Imaging / Q000379:methods*; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D011877:Radionuclide Imaging / Q000379:methods*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000493:pharmacokinetics
D007457:Iodine Radioisotopes; D019716:Tissue Inhibitor of Metalloproteinase-2; D020781:Matrix Metalloproteinase 1