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 comprising:
2. 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.
3. 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.
4. The liposomal composition of claim 1 , the membrane further comprising:
a phospholipid;
cholesterol;
a nonradioactive MM contrast enhancing agent comprising gadolinium; and
1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000].
5. The liposomal composition of claim 1 , the phospholipid-polymer moiety in the phospholipid-polymer-aromatic conjugate being represented by the following structural formula:
or a salt thereof, wherein m is one of 12, 13, 14, 15, 16, 17, or 18, and wherein n is an integer between 60 and 100.
6. The liposomal composition of claim 5 , wherein m is 16.
7. The liposomal composition of claim 5 , wherein n is an integer between 70 and 90.
8. The liposomal composition of claim 5 , wherein n is 79.
9. 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 comprising:
a nonradioactive magnetic resonance imaging (MM) contrast enhancing agent at least one of encapsulated by or bound to the membrane; and
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.
10. The kit of claim 9 , the phospholipid-polymer moiety in the phospholipid-polymer-aromatic conjugate being represented by the following structural formula:
or a salt thereof, wherein m is one of 12, 13, 14, 15, 16, 17, or 18, and wherein n is an integer between 60 and 100.
11. The kit of claim 10 , wherein m is 16.
12. The kit of claim 10 , wherein n is an integer between 70 and 90.
13. The kit of claim 10 , the membrane further comprising:
a phospholipid;
cholesterol; and
1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000].
14. 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 comprising:
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.
15. The method of claim 14 , the detecting comprising detecting using magnetic resonance imaging.
16. The method of claim 14 , the MRI contrast enhancing agent comprising gadolinium.
17. The method of claim 16 , the liposomal composition characterized by per-particle relaxivity in mM-1 s-1 at 1 T of at least about: 190,000.
18. The method of claim 14 , the membrane further comprising:
a phospholipid;
cholesterol;
a nonradioactive MRI contrast enhancing agent comprising gadolinium; and
1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000].
19. The method of claim 14 , further comprising diagnosing the patient with Alzheimer's disease according to detecting the liposomal composition associated with the one or more amyloid deposits.
20. The method of claim 14 , 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.