US 20110250145A1

(19) United States (12) Patent Application Publication (10) Pub. No.: US 2011/0250145 A1
Sharma et al.

(43) Pub. Date:

Oct. 13, 2011

(54)

BIOLUMINESCENCE IMAGING OF

Related US. Application Data

(60) Provisional application No. 61/ 1 10,727, ?led on Nov. 3, 2008.
Publication Classi?cation

MYELOPEROXIDASE ACTIVITY IN VIVO, METHODS, COMPOSITIONS AND

APPARATUSES THEREFOR

(75)

Inventors:

Vij ay Sharma, WildWood, MO (US); Seth Gammon, St. Louis, MO (US); David PiWnica-Worms, Ladue, MO (US); Shimon Gross, Yavne (IL)

(51)

Int. Cl. A61K 49/00 C07D 413/14 C07D 405/12 C07D 403/14 C07D 237/32 C07D 491/22

(2006.01) (2006.01) (2006.01) (2006.01) (2006.01) (2006.01)

(73) Assignee: (21) Appl. No.: (22) (86)

PCT Filed:
PCT No.:

Washington University, St. Louis, MO (US)

(52)

US. Cl. ........................................ .. 424/9.6; 544/237

(57) ABSTRACT Methods of imaging distribution of myeloperoxidase activity

in a subject are disclosed. These methods include the use of

13/127,448
Nov. 3, 2009
PCT/US2009/063186

bioluminescent substrates, including luminol and Wave

length-shifted analogues of luminol. Bioluminescent

myeloperoxidase substrates that emit light at longer Wave lengths compared to luminol are shoWn to be useful for imag

ing myeloperoxidase activity in vivo. The disclosed methods

371 (0X1), (2), (4) Date:

can be used for imaging sites of in?ammation and other pathological conditions associated With abnormal levels of MPO activity in vivo. Methods of synthesis of luminol ana
logues are also disclosed.

Jun. 22, 2011

Patent Application Publication

Oct. 13, 2011 Sheet 1 0f 24

US 2011/0250145 A1

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Oct. 13, 2011 Sheet 10 0f 24

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