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US 2013/0259805 A1Published application
Development and screening of contrast agents for in vivo imaging of parkinson's disease
AssigneeThe General Hospital Corporation
InventorBrian Bacskai
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Abstract
The invention provides compounds and a method for imaging aggregated α-synuclein, e.g., Lewy bodies or Lewy neurites, in a tissue or organ.
Claims21
A method for in vivo imaging of an α-synuclein aggregate, the method comprising:
- a) administering, to a subject in need thereof, a detectable amount of a compound selected from the group consisting of 3,3′-diethylthiadicarbocyanine iodide (3-3′-DTDCI);
- 4-[4-[4-(dimethylamino)phenyl]-1,3-butadienyl]-1-ethyl-pyridinium perchlorate (LDS 722);
- LDS 759;
- 4-[4-[4-(dimethylamino)phenyl]-1,3-butadienyl]-1-ethyl quinolinium (LDS 798);
- NIAD-1;
- 9-diethylamino-5-benzo[α]phenoxazinone (Nile Red);
- RD-1;
- THK-265;
- 2-[4-[4-(dimethylamino)phenyl]-1,3-butadienyl]-1,3,3-trimethyl-3H-indolium perchlorate (LDS 730);
- 5-amino-9-(diethylamino)-benzo[a]phenoxazin-7-ium perchlorate (Nile Blue 690 ClO4);
- 2-[7-(1,3-dihydro-1,3,3-trimethyl-2H-indol-2-ylidene)-1,3,5-heptatrienyl]-1,3,3-trimethyl-3H-indolium perchlorate (HITC ClO4);
- 2,2″-([1,1′-biphenyl]-4.4′-diyldi-2,1-ethenediyl)bis-benzenesulfonic acid disodium salt (Stilbene 420);
- analogs, derivatives, isomers and pharmaceutically acceptable salts thereof;
- and any combinations thereof;
- and
- b) detecting the contrast agent bound to the α-synuclein aggregate to image the α-synuclein aggregate.
13 more elements
A method for detecting, diagnosing, or determining regression, progression, or onset of a Lewy body or Lewy neurite associated disorder, the method comprising:
- a) administering, to a subject in need thereof, a detectable amount of a compound selected from the group consisting of 3-3′-DTDCI, LDS 722, LDS 759, LDS 798, NIAD-1, Nile Red, RD-1, THK-265, LDS 730, Nile Blue 690 ClO4, HITC ClO4, Stilbene 420, and any combinations thereof;
- and
- b) detecting the compound bound to α-synuclein aggregate to determine the level of binding of the contrast agent, wherein an increase in the level of binding relative to a control level of binding indicates that the subject is suffering from or is at risk of developing an α-synuclein aggregate associated disorder.
A method of evaluating a treatment for a Lewy body or Lewy neurite associated disorder, the method comprising:
- a) administering a first detectable amount of a compound to a subject undergoing treatment for a Lewy body or Lewy neurite associated disorder to obtain a first level of binding of the compound to α-synuclein aggregate in the subject;
- b) detecting the compound bound to α-synuclein aggregate to determine the first level of binding of the compound;
- c) administering a second detectable amount of the compound, wherein the second administration is at a time subsequent to the first administration, to obtain a second level of binding of the compound to α-synuclein aggregate in the subject;
- d) detecting the compound bound to α-synuclein aggregate to determine the second level of binding of the compound;
- and
- e) comparing the first level of binding with the second level of binding as an indication of the effectiveness of the treatment on the level of α-synuclein aggregate in the subject, wherein the compound is selected from the group consisting of 3-3′-DTDCI, LDS 722, LDS 759, LDS 798, NIAD-1, Nile Red, RD-1, THK-265, LDS 730, Nile Blue 690 ClO4, HITC ClO4, Stilbene 420, and any combinations.
3 more elements
A method of detecting α-synuclein aggregates in a tissue, the method comprising:
- a) contacting a compound with a tissue, wherein the contrast agent is selected from the group consisting of 3-3′-DTDC1, LDS 722, LDS 759, LDS 798, NIAD-1, Nile Red, RD-1, THK-265, LDS 730, Nile Blue 690 ClO4 HITC ClO4, Stilbene 420, and any combinations thereof;
- and
- b) detecting the compound bound to α-synuclein aggregate to determine the level of binding of the compound, wherein the level of biding indicates the amount of α-synuclein aggregate in the tissue.
(canceled)
Dependencies are inferred from the claim text.