Metal oxides nanoparticles conjugated with naphthalene derivatives as contrast agents for the detection of beta amyloid plaques by magnetic resonance images

A magnetic nanoparticle related to the agglomerates and β-amyloid plaques for the diagnosis of Alzheimer's disease by magnetic resonance imaging, characterized by compounds of Formula I comprising a metal oxide core coated with a multifunctional organic layer, wherein said organic layer is conjugated with a naphthyl compound,

• wherein:
• R1:
• is an organic coating to the metal oxide core, of polymeric type selected from the group polyethylene glycol (PEG), amino-PEG, PEG-carboxyl acid, amino-PEG-carboxyl acid, PEG-di carboxyl acid, PEG-polylactic acid, and PEG-polylactic-co-glycolic acid;
• R2:
• is —NHCO-alkylenyl-C(O)NH-alkylenyl-R3;
• R3:
• is —COO—, —CO—, —NH, —O—, —S—, —NH-alkylenyl-NH—, —NR4—CSS—;
• R4:
• is —H, —CH3, —CH2—CH3, —CH2CH2CH3, and
• MxOy:
• is iron oxide (Fe3O4/γFe2O3), gadolinium oxide(III), manganese oxide(II) or copper(II) oxide;
• wherein the naphthyl compound is selected from the group:
• N1-(2-aminoethyl)-N4-(1-naphthyl)succinamide, N-[4-(1-naphthylamino)-4-oxobutanoyl]-β-alanine, 6-{[4-(1-naphthylamino)-4-oxobutanoyl]amino}hexanoic acid, N1-(2-aminobutyl)-N4-(1-naphthyl)succinamide, N-(2-hydroxyethyl)-N′-1-naphthyl succinamide, N-(3-mercaptopropyl)-N′-1-naphthysuccinamide, N-{2-[(2-aminoethyl)amino]ethyl}-N′-1-naphthysuccinamide and (2-{[4-(1-naphthylamino)-4-oxobutanoyl]amino}ethyl)carbamodithioic acid sodium salt;
• wherein the alkylenyl term in R2 and R3 is selected from the group consisting of ethylenyl (—CH2CH2—), butylenyl (—CH2CH2CH2CH2—) and hexylenyl (—CH2CH2CH2CH2CH2CH2—);
• wherein the conjugated, functionalized and coated magnetic nanoparticle is capable of, when it is administered to a mammal, crossing the blood-brain barrier and specifically binding to the agglomerates and β-amyloid plaques present in brain tissue;
• wherein, with the nanoparticle bound to the agglomerates and β-amyloid plaques in the brain tissue, hypo- or hyper-intense signals are observed in the region of interest through magnetic resonance imaging.