Psma targeted fluorescent agents for image guided surgery

Patent metadata

Field	Value
Publication number	US-2017283384-A1
Application number	US-201715618788-A
Country	US
Kind code	A1
Filing date	Jun 9, 2017
Priority date	Mar 19, 2009
Publication date	Oct 5, 2017
Grant date	—

Abstract

Compositions and methods for visualizing tissue under illumination with near-infrared radiation, including compounds comprising near-infrared, closed chain, sulfo-cyanine dyes and prostate specific membrane antigen ligands are disclosed.

First claim

That which is claimed:

1 . A compound of the following formula:

or a pharmaceutically acceptable salt thereof.

2 . A composition comprising compound (3):

or a pharmaceutically acceptable salt thereof;
wherein the composition is adapted for visualization of tissue under illumination with near-infrared radiation.

3 . The composition of claim 2 , wherein the composition is adapted for administration to a subject.

4 . The composition of claim 3 , wherein the composition comprises a unit dosage form of compound (3).

5 . The composition of claim 4 , wherein the unit dosage form delivers to the subject an amount of compound (3) between about 0.01 and about 8 mg/kg.

6 . The composition of claim 5 , wherein the unit dosage form delivers to the subject an amount of compound (3) of about 0.01 mg/kg, about 0.05 mg/kg, about 0.10 mg/kg, about 0.20 mg/kg, about 0.3 mg/kg, about 0.35 mg/kg, about 0.40 mg/kg, about 0.45 mg/kg, about 0.50 mg/kg, about 0.55 mg/kg, about 0.60 mg/kg, about 0.65 mg/kg, about 0.70 mg/kg, about 0.75 mg/kg, about 0.80 mg/kg, about 0.90 mg/kg, about 1 mg/kg, about 2, mg/kg, about 4 mg/kg, about 6 mg/kg, or about 8 mg/kg.

7 . The composition of claim 2 , wherein the composition is in a single dose form.

8 . The composition of claim 2 , wherein the composition is in dry form.

9 . The composition of claim 2 , wherein the composition is lyophilized in a sterile container.

10 . The composition of claim 2 , wherein the composition is contained within a sterile container.

11 . The composition of claim 10 , wherein the sterile container comprises a machine detectable identifier.

12 . The composition of claim 2 , further comprising one or more pharmaceutically acceptable excipients in an oral dosage form.

13 . The composition of claim 2 , further comprising one or more pharmaceutically acceptable carriers in an injectable dosage form.

14 . The composition of claim 2 , further comprising one or more pharmaceutically acceptable excipients in a dosage form for direct delivery to a surgical site.

15 . The use of a composition of claim 2 for administration to a subject to obtain visualization of tissue expressing PSMA under illumination with near-infrared radiation.

16 . The use of claim 15 , wherein the subject is a human subject.

17 . A method for visualization of tissue expressing PSMA, the method comprising administering to a subject a composition comprising compound (3):

or a pharmaceutically acceptable salt thereof;
wherein compound (3) is administered in an amount sufficient for imaging tissue under illumination with near-infrared radiation;
imaging the tissue under illumination with near-infrared radiation; and
obtaining at least one image of tissue from the subject.

18 . The method of claim 17 , wherein the composition comprises a unit dosage form of compound (3).

19 . The method of claim 18 , wherein the unit dosage form delivers to the subject an amount of compound (3) from about 0.01 mg/kg and about 8 mg/kg.

20 . The method of claim 18 , wherein the composition is sterile, non-toxic, and adapted for administration to a subject.

21 . The method of claim 17 , further comprising obtaining the image during administration, after administration, or both during and after administration of the composition.

22 . The method of claim 17 , further comprising intravenously injecting a composition comprising compound (3) into the subject.

23 . The method of claim 22 , wherein the composition is injected into a circulatory system of the subject.

24 . The method of claim 17 , further comprising visualizing a subject area on which surgery is or will be performed.

25 . The method of claim 24 , further comprising performing a surgical procedure of the subject area based on the visualization of the area.

26 . The method of claim 24 , further comprising viewing a subject area on which an ophthalmic, arthroscopic, laparoscopic, cardiothoracic, muscular, or neurological procedure is or will be performed.

27 . The method of claim 17 , further comprising diagnosing the subject with a condition or disease based on the visualization of the tissue expressing PSMA.

28 . The method of claim 17 , further comprising obtaining ex vivo images of at least a portion of the subject.

29 . The method of claim 17 , wherein the tissue being visualized comprises tumor tissue.

30 . The method of claim 17 , wherein the tissue being visualized comprises cancerous tissue.

31 . The method of claim 17 , wherein the tissue being visualized comprises prostate tissue.

32 . The method of claim 17 , wherein the tissue being visualized comprises prostate tumor tissue.

33 . The method of claim 17 , wherein the tissue being visualized comprises nerve tissue.

34 . The method of claim 17 wherein the tissue being visualized comprises clear cell renal cell carcinoma.

Assignees

• Univ Johns Hopkins
• Intuitive Surgical Operations

Inventors

• Pomper Martin G
• Mease Ronnie C
• Chen Ying
• Ray Sangeeta
• Sorger Jonathan

Classifications

• C07F5/027

  Organoboranes and organoborohydrides · CPC title

• C07D213/04

  having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom · CPC title

• C07D209/24

  with an alkyl or cycloalkyl radical attached to the ring nitrogen atom · CPC title

• C07D249/04

  1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles · CPC title

• C07D311/20

  hydrogenated in the hetero ring · CPC title