title: (99m)Tc-MAG3-aptamer for imaging human tumors associated with high level of matrix metalloprotease-9.
abstract: The human matrix metalloprotease 9 (hMMP-9) is involved in many physiological processes such as tissue remodeling. Its overexpression in tumors promotes the release of cancer cells thus contributing to tumor metastasis. It is a relevant marker of malignant tumors. We selected an RNA aptamer containing 2'-fluoro, pyrimidine ribonucleosides, that exhibits a strong affinity for hMMP-9 (K(d) = 20 nM) and that discriminates other human MMPs: no binding was detected to either hMMP-2 or -7. Investigating the binding properties of different MMP-9 aptamer variants by surface plasmon resonance allowed the determination of recognition elements. As a result, a truncated aptamer, 36 nucleotides long, was made fully resistant to nuclease following the substitution of every purine ribonucleoside residue by 2'-O-methyl analogues and was conjugated to S-acetylmercaptoacetyltriglycine for imaging purposes. The resulting modified aptamer retained the binding properties of the originally selected sequence. Following (99m)Tc labeling, this aptamer was used for ex vivo imaging slices of human brain tumors. We were able to specifically detect the presence of hMMP-9 in such tissues.
authors.affiliation: INSERM U869, ARNA, Institut Européen de Chimie et Biologie, 33607 Pessac, France.
authors.forename: Sonia
authors.initials: S
authors.lastname: Da Rocha Gomes
authors.forename: Julie
authors.initials: J
authors.lastname: Miguel
authors.forename: Laurent
authors.initials: L
authors.lastname: Azéma
authors.forename: Sandrine
authors.initials: S
authors.lastname: Eimer
authors.forename: Colette
authors.initials: C
authors.lastname: Ries
authors.forename: Eric
authors.initials: E
authors.lastname: Dausse
authors.forename: Hugues
authors.initials: H
authors.lastname: Loiseau
authors.forename: Michèle
authors.initials: M
authors.lastname: Allard
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Toulmé
mesh_terms: D052157:Aptamers, Nucleotide / Q000138:chemical synthesis / Q000737:chemistry; D006801:Humans; D007150:Immunohistochemistry; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D015394:Molecular Structure; D009369:Neoplasms / Q000175:diagnosis* / Q000201:enzymology* / Q000378:metabolism; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry; D017263:Technetium Tc 99m Mertiatide / Q000138:chemical synthesis / Q000737:chemistry
chemical_list: D052157:Aptamers, Nucleotide; D019275:Radiopharmaceuticals; D017263:Technetium Tc 99m Mertiatide; D020780:Matrix Metalloproteinase 9