MRI imaging of amyloid plaque using liposomes
Provided are aromatic compounds, phospholipid-polymer-aromatic conjugates comprising the aromatic compounds, and liposome compositions including the phospholipid-polymer-aromatic conjugates. The liposomal compositions may be useful for imaging of Alzheimer's Disease, for example, imaging of the amyloid-β plaque deposits characteristic of Alzheimer's Disease.
1. A liposomal composition, comprising:
a membrane, comprising:
a phospholipid-polymer-aromatic conjugate, the aromatic moiety in the phospholipid-polymer-aromatic conjugate being represented by:
wherein:
R 2 is a linking group comprising 1 to 6 carbon atoms that is one of: alkylene or alkoxyalkylene.
2. The liposomal composition of claim 1 , the aromatic moiety in the phospholipid-polymer-aromatic conjugate being represented by
3. The liposomal composition of claim 1 , the phospholipid-polymer moiety in the phospholipid-polymer-aromatic conjugate being represented by one of the following structural formula:
n being an integer from about 60 to about 100; and
m being one of: 12, 13, 14, 15, 16, 17, or 18.
4. The liposomal composition of claim 1 , further comprising a nonradioactive magnetic resonance imaging (MRI) contrast enhancing agent that is at least one of encapsulated by or bound to the membrane.
5. The liposomal composition of claim 1 , the membrane further comprising a first phospholipid and a second phospholipid, the second phospholipid being derivatized with a hydrophilic polymer.
6. The liposomal composition of claim 1 , the membrane further comprising:
DPPC;
cholesterol;
diethylenetriaminepentaacetic acid)-bis(stearylamide), gadolinium salt; and
1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000].
7. A method for imaging amyloid deposits in a patient, the method comprising:
introducing into the patient a detectable quantity of a liposomal composition, the liposomal composition comprising:
a membrane, comprising:
a phospholipid-polymer-aromatic conjugate, the aromatic moiety in the phospholipid-polymer-aromatic conjugate being represented by:
wherein:
R 2 is a linking group comprising 1 to 6 carbon atoms that is one of:
alkylene or alkoxyalkylene;
a nonradioactive magnetic resonance imaging (MM) contrast enhancing agent at least one of encapsulated by or bound to the membrane;
allowing sufficient time for the liposomal composition to be associated with one or more amyloid deposits; and
detecting the liposomal composition associated with the one or more amyloid deposits.
8. The method of claim 7 , the detecting comprising detecting using magnetic resonance imaging.
9. The method of claim 7 , the nonradioactive magnetic resonance imaging (MM) contrast enhancing agent being encapsulated by and bound to the membrane.
10. The method of claim 9 , the liposomal composition characterized by per-particle relaxivity in mM −1 s −1 of at least about one or more of about: 100,000, 125,000, 150,000, 165,000, 180,000, 190,000, and 200,000.
11. The method of claim 7 , the aromatic moiety in the phospholipid-polymer-aromatic conjugate being represented
12. The method of claim 7 , the membrane further comprising:
DPPC;
cholesterol;
diethylenetriaminepentaacetic acid)-bis(stearylamide), gadolinium salt; and
1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000].
13. The method of claim 7 , further comprising diagnosing the patient with Alzheimer's disease according to detecting the liposomal composition associated with the one or more amyloid deposits.
14. The method of claim 7 , further comprising:
identifying the patient as potentially having Alzheimer's disease according to detecting the liposomal composition associated with the one or more amyloid deposits;
subjecting the patient to an analysis for tau neurofibrillary tangles; and
upon determining the presence of tau neurofibrillary tangles in conjunction with detecting the liposomal composition associated with the one or more amyloid deposits, diagnosing the patent with Alzheimer's disease.
15. A kit for imaging amyloid deposits in a patient, the kit comprising:
a liposomal composition, the liposomal composition comprising:
a membrane, comprising:
a phospholipid-polymer-aromatic conjugate, the aromatic moiety in the phospholipid-polymer-aromatic conjugate being represented by:
wherein:
R 2 is a linking group comprising 1 to 6 carbon atoms that is one of:
alkylene or alkoxyalkylene;
a nonradioactive magnetic resonance imaging (MM) contrast enhancing agent at least one of encapsulated by or bound to the membrane;
Instructions, the instructions directing a user to
introduce into the patient a detectable quantity of the liposomal composition;
allow sufficient time for the liposomal composition to be associated with one or more amyloid deposits; and
detect the liposomal composition associated with the one or more amyloid deposits.
16. The kit of claim 15 , the instructions further directing the user to diagnose the patient with Alzheimer's disease according to detection of the liposomal composition associated with the one or more amyloid deposits.
17. The kit of claim 15 , the aromatic moiety in the phospholipid-polymer-aromatic conjugate being represented by
18. The liposomal composition of claim 1 , wherein the phospholipid-polymer-aromatic conjugate comprises a compound having the formula:
n being an integer from about 70 to about 90; and
m being 14 or 16.