Use of perfluoroalkyl-containing metal complexes as contrast media for diagnosis of Alzheimer's disease
The invention relates to the use of metal complexes that contain at least one perfluorinated alkyl radical and at least one chelating agent radical and at least one metal ion equivalent of the atomic numbers 21-29, 31-33, 37-39, 42-44, 49 or 57-83, as well as salts thereof for the production of a diagnostic agent for visualizing amyloid-containing plaques.
1 . A method of diagnosing for the production of amyloid-containing plaques in a sample comprising contacting said sample with a metal chelate containing
at least one perfluorinated alkyl radical, and
at least one chelating agent radical, and
at least one metal ion equivalent of atomic numbers 21-29, 31-33, 37-39, 42-44, 49 or 57-83, as well as salts thereof.
2 . A method according to claim 1 , characterized in that the metal chelates or salts thereof contain
1 perfluorinated alkyl radical, and
1 or 2 chelating agent radicals.
3 . A method according to claim 1 , wherein the perfluorinated alkyl radical contains 4-30 C atoms, preferably 6-20 C atoms.
4 . A method according to claim 1 , wherein the metal ion is paramagnetic.
5 . A method according to claim 4 , wherein the metal complexes contain at least a divalent or trivalent ion of the elements of atomic numbers 21-29, 42, 44 and 58-70.
6 . A method according to claim 4 , wherein the metal complexes or salts thereof have
a critical micelle formation concentration<10 −3 mol/l,
a hydrodynamic micelle diameter (2 Rh)>1 nm, and
a proton relaxivity in plasma (R 1 )>10 l/mmol*s.
7 . A method according to claim 4 , wherein the metal complexes are used as MRI contrast media for diagnosis of Alzheimer's disease in a patient.
8 . A method according to claim 1 , wherein the metal complexes are used as contrast media for differentiation between Alzheimer's disease and other dementia diseases in a patient.
9 . A method according to claim 1 , wherein the metal complexes are used as contrast media for early detection of Alzheimer's disease in a patient.
10 . A method according to claim 1 , wherein the metal complexes are used as contrast media for monitoring the course of treatment in treated Alzheimer patients.
11 . A method according to claim 1 , wherein the metal complexes are used as contrast media for identifying patients at risk for developing Alzheimer's disease.
12 . A method according to claim 6 , wherein metal complexes are used whose micelle formation concentration is <10 −4 mol/l.
13 . A method according to claim 6 , wherein metal complexes are used whose hydrodynamic micelle diameter is ≧3 nm, preferably >4 nm.
14 . A method according to claim 4 , wherein metal complexes are used that have a proton relaxivity in the plasma of >13 l/mmol*s, preferably >15 l/mmol*s.
15 . A method according to claim 1 , wherein the metal complexes overcome the blood-brain barrier.
16 . A method according to claim 1 , wherein the metal complexes contain at least one divalent or trivalent ion of the elements of atomic numbers 25, 26, 39 or 57-83.
17 . A method according to claim 16 for use in x-ray diagnosis.
18 . A method of visualizing amyloid-containing plaques in a sample in particular for use in SPECT, PET, 18 F-MRI or optical imaging comprising contacting said sample with a metal chelate containing
at least one perfluorinated alkyl radical, and
at least one chelating agent radical, and
at least one metal ion equivalent of the atomic numbers 21-29, 31-33, 37-39, 42-44, 49 or 57-83, as well as salts thereof,
and a signaling group.
19 . Process for the in-vitro detection of amyloid plaques and/or the in-vitro diagnosis of Alzheimer's disease containing the following steps:
(a) Incubation of a metal complex that can be used according to the invention, with optionally preferred and/or fixed cerebral tissue of patients;
(b) Detection of amyloid plaques and/or localization and/or quantification of amyloid plaques with a suitable detection method, in particular selected from MR spectroscopy, MRI, and x-ray-based methods.
20 . Process for the in-vitro detection of amyloid plaques and/or the in-vitro diagnosis of Alzheimer's disease containing the following steps:
(a) Incubation of a metal complex that can be used according to the invention, containing a signaling group, with optionally pretreated and/or fixed cerebral tissue of patients, as well as
(b) Detection of amyloid plaques and/or localization and/or quantification of amyloid plaques with a suitable detection method.