Light sensitive compounds for instant determination of organ function

• US 20040213740A1
• Filed: 01/02/2004
• Published: 10/28/2004
• Est. Priority Date: 10/16/2000
• Status: Active Grant

• Current Assignee: Mallinckrodt Incorporated (Mallinckrodt plc)
• Original Assignee: Mallinckrodt Incorporated (Mallinckrodt plc)
• Inventors: Rajagopalan, Raghavan, Dorshow, Richard B., Achilefu, Samuel, Bugaj, Joseph E., Periasamy, Muthunadar P., Jimenez, Hermo N.
• Granted Patent: US 7,175,831 B2
• Time in Patent Office: Days
• US Class Current: 424/9.6
• CPC Class Codes: A61K 49/0032 Methine dyes, e.g. cyanine dyes
• CPC Class Codes: C09B 23/02 the polymethine chain containing an odd number of >CH- or >C[alkyl]- groups

Abstract

Highly hydrophilic indole and benzoindole derivatives that absorb and fluoresce in the visible region of light are disclosed. These compounds are useful for physiological and organ function monitoring. Particularly, the molecules of the invention are useful for optical diagnosis of renal and cardiac diseases and for estimation of blood volume in vivo.

Claims

1. A pharmaceutical composition comprising an effective amount of the compound of formula 4

5. The composition as in claims 1, 2, 3, or 4 further comprising a contrast agent.

6. The composition as in claims 1, 2, 3, or 4 wherein the compound comprises a radioactive halogen.

7. The composition as in claims 1, 2, 3, or 4 wherein at least one R group of the compound is replaced by a polyamino carboxylic acid or its derivative.

8. The composition of claim 7 further comprising a radioactive metal ion or a paramagnetic metal ion.

9. The composition as in claims 1, 2, 3, 4, 6, or 7 formulated as at least one of a liposome, a micell, a microcapsule, or a microparticle.

10. The composition as in claims 1, 2, 3, 4, 6, or 7 formulated as at least one of ultra small iron oxide particles, silver particles, or gold particles.

29. The method of imaging a patient comprising administering a non-optical contrast agent composition further comprising the compound as in claims 1, 2, 3, 4, 7, or 8 and performing at least one of an optical imaging procedure or a non-optical imaging procedure.

30. The method of claim 29 wherein the non-optical contrast agent composition is chosen from a magnetic resonance composition, a computed tomography composition, an x-ray composition, a nuclear imaging composition, a positron emission tomography composition, a single photon emission computed tomography composition, an optoacoustic imaging composition and an ultrasound composition.

31. The method of claim 29 wherein the compound stabilizes or buffers the non-optical contrast agent composition.

2. A pharmaceutical composition comprising an effective amount of the compound of formula 4

3. A pharmaceutical composition comprising an effective amount of the compound of formula 4

4. A pharmaceutical composition comprising an effective amount of the compound of formula 4

11. A method for performing a diagnostic or therapeutic procedure comprising administering to a mammal an effective amount of the compound of formula 4

15. The method as in claims 11, 12, 13, or 14 wherein said procedure utilizes light of wavelength in the region of 350-1300 nm.

16. The method of claim 15 wherein said procedure comprises monitoring a blood clearance profile by fluorescence using light of wavelength in the region of 350 nm to 1300 nm.

17. The method as in claims 11, 12, 13, or 14 wherein said procedure comprises monitoring a blood clearance profile by absorption using light of wavelength in the region of 350 nm to 1300 nm.

18. The method as in claims 11, 12, 13, or 14 wherein the compound contains a radioactive halogen and imaging the mammal by at least one of optical imaging and nuclear imaging.

19. The method as in claims 11, 12, 13, or 14 where the compound administered has at least one R group replaced by a polyamino carboxylic acid or its derivative.

20. The method as in claims 11, 12, 13, or 14 wherein the compound administered further comprises a radioactive metal ion or a paramagnetic metal ion.

21. The method as in claims 11, 12, 13, 14, 19, or 20 further comprising imaging by at least one of optical imaging, nuclear imaging, or magnetic resonance imaging.

22. The method as in claims 11, 12, 13, 14, or 19 wherein the compound is administered in a formulation selected from at least one of liposomes, micelles, microcapsules, or microparticles.

23. The method as in claims 11, 12, 13, 14, 18, 19, or 20 wherein the compound is administered in a formulation selected from at least one of ultra small iron oxide particles, silver particles, or gold particles.

24. The method as in claims 11, 12, 13, 14, 18, 19, 20, 21, 22, or 23 further comprising administering a non-optical contrast agent and imaging by at least one of magnetic resonance, ultrasound, x-ray, positron emission tomography, computed tomography, optoacoustic imaging, and single photon emission computed tomography.

25. The method as in claims 11, 12, 13, 14, 18, 19, 20, 21, 22, or 23 wherein said procedure is for physiological function monitoring.

26. The method as in claims 11, 12, 13, 14, 18, 19, 20, 21, 22, or 23 wherein said procedure is for at least one of renal function monitoring, cardiac function monitoring, and kidney function monitoring.

27. The method as in claims 11, 12, 13, 14, 18, 19, 20, 21, 22, or 23 wherein said procedure is for determining organ perfusion in vivo.

28. The method as in claims 11, 12, 13, 14, 18, 19, 20, 21, 22, or 23 further comprising optically imaging the mammal.

12. A method for performing a diagnostic or therapeutic procedure comprising administering to a mammal an effective amount of the compound of formula 4

13. A method for performing a diagnostic or therapeutic procedure comprising administering to a mammal an effective amount of the compound of formula 4

14. A method for performing a diagnostic or therapeutic procedure comprising administering to a mammal an effective amount of the compound of formula 4