title: New enzyme-activated solubility-switchable contrast agent for magnetic resonance imaging: from synthesis to in vivo imaging.
abstract: We designed and synthesized a novel contrast agent (CA) to image the activity of matrix metalloproteinase-2 (MMP-2) in a tumor, noninvasively using magnetic resonance imaging (MRI). We exploited the concept of solubility-switchable CAs in the design of a protease-modulated CA (PCA), referred to as PCA2-switch. This PCA contains a paramagnetic gadolinium chelate (Gd-DOTA), which was attached to the N-terminus of a MMP-2 cleavable peptide sequence via a hydrophobic chain. The aqueous solubility of the CA depends on the presence of a polyethylene glycol chain (PEG) on the C-terminus of the peptide. Upon proteolytic cleavage of the peptide by MMP-2, the PEG chain is detached from the CA, which becomes less water soluble. This compound and control compounds were successfully tested in an animal model bearing two tumors with different levels of MMP-2 activity.
authors.affiliation: Centre d'Imagerie Moleculaire de Sherbrooke and Department of Nuclear Medicine and Radiobiology, Universite de Sherbrooke, 3001 12e Avenue Nord, Sherbrooke, Quebec J1H 5N4, Canada.
authors.forename: Beata
authors.initials: B
authors.lastname: Jastrzebska
authors.forename: Réjean
authors.initials: R
authors.lastname: Lebel
authors.forename: Hélène
authors.initials: H
authors.lastname: Therriault
authors.forename: J Oliver
authors.initials: JO
authors.lastname: McIntyre
authors.forename: Emanuel
authors.initials: E
authors.lastname: Escher
authors.forename: Brigitte
authors.initials: B
authors.lastname: Guérin
authors.forename: Benoit
authors.initials: B
authors.lastname: Paquette
authors.forename: Witold A
authors.initials: WA
authors.lastname: Neugebauer
authors.forename: Martin
authors.initials: M
authors.lastname: Lepage
mesh_terms: D000818:Animals; D003287:Contrast Media; D006571:Heterocyclic Compounds; D008279:Magnetic Resonance Imaging; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D051379:Mice; D009374:Neoplasms, Experimental / Q000201:enzymology; D009942:Organometallic Compounds; D012995:Solubility; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D003287:Contrast Media; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; C050823:gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate; D020778:Matrix Metalloproteinase 2