Claims
- 1. A compound of formula
- 2. The compound of claim 1 wherein W4 and X4 are independently selected from the group consisting of —NR3 and —S—; Y4 is selected from the group consisting of —(CH2)a—CONH-Bm, —CH2—(CH2OCH2)b—CH2—CONH-Bm, —(CH2)a—NHCO-Bm, —CH2—(CH2OCH2)b—CH2—NHCO-Bm, —(CH2)a—NR3R4, and —CH2(CH2OCH2)b—CH2NR3R4; Z4 is selected from the group consisting of —(CH2)a—CONH-Dm, —CH2—(CH2OCH2)b—CH2—CONH-Dm, —(CH2)a—NHCO-Dm, —CH2—(CH2OCH2)b—CH2—NHCO-Dm, —(CH2)a—NR3R4, and —CH2(CH2OCH2)b—CH2NR3R4; A2 is a single or a double bond; B2, C2, and D2 are independently selected from the group consisting of —O—, —S—, NR3, (CH2)a—CR1R2, and —CR1; A2, B2, C2, and D2 may together form a 6- to 10-membered carbocyclic ring or a 6- to 10-membered heterocyclic ring optionally containing one or more oxygen, nitrogen, or sulfur atom; a4 and b4 are independently from 0 to 3; R1 to R4, and R45 to R57 are independently selected from the group consisting of hydrogen, C1-C10 alkyl, C5-C12 aryl, C1-C10 alkoxyl, C1-C10 polyhydroxyalkyl, C5-C12 polyhydroxyaryl, C1-C10 aminoalkyl, mono- or oligosaccharide, peptide with 2 to 30 amino acid units, —CH2(CH2OCH2)b—CH2—OH, —(CH2)a—CO2H, —(CH2)a—CONH-Bm, —CH2—(CH2OCH2)b—CH2—CONH-Bm, —(CH2)a—NHCO-Bm, —CH2—(CH2OCH2)b—CH2—NHCO-Bm, —(CH2)a—OH and —CH2—(CH2OCH2)b—CO2H; Bm and Dm are independently selected from the group consisting of a bioactive peptide containing 2 to 30 amino acid units, an antibody, a mono- or oligosaccharide, a glycopeptide, a metal chelating agent, a radioactive or nonradioactive metal complex, and an echogenic agent; a and c are independently from 1 to 10; and b and d are independently from 1 to 30.
- 3. The compound of claim 1 wherein each W4 and X4 is C(CH3)2; Y4 is —(CH2)2—CONH-Bm; Z4 is —(CH2)2—CONH-Dm; A2 is a single bond; A2, B2, C2, and D2 together form a 6-membered carbocyclic ring; each a4 and b4 is 1; R45 is galactose; each R46 to R57 is hydrogen; Bm is Octreotate; Dm is bombesin (7-14).
- 4. The compound of claim 1 further comprising one to ten groups containing Bm, Dm, and combinations thereof wherein W4 and X4 additionally include CR1R2.
- 5. The compound of claim 4 wherein a porphyrin or a photodynamic therapy agent is attached to Bm, Dm, and combinations thereof.
- 6. A composition comprising a cyanine dye bioconjugate of formula
- 7. The composition of claim 6 wherein W4 and X4 are independently selected from the group consisting of —NR3 and —S—; Y4 is selected from the group consisting of —(CH2)a—CONH-Bm, —CH2—(CH2OCH2)b—CH2—CONH-Bm, —(CH2)a—NHCO-Bm, —CH2—(CH2OCH2)b—CH2—NHCO-Bm, —(CH2)a—NR3R4, and —CH2(CH2OCH2)b—CH2NR3R4; Z4 is selected from the group consisting of —(CH2)a—CONH-Dm, —CH2—(CH2OCH2)b—CH2—CONH-Dm, —(CH2)a—NHCO-Dm, —CH2—(CH2OCH2)b—CH2—NHCO-Dm, —(CH2)a—NR3R4, and —CH2(CH2OCH2)b—CH2NR3R4; A2 is a single or a double bond; B2, C2, and D2 are independently selected from the group consisting of —O—, —S—, NR3, (CH2)a—CR1R2, and —CR1; A2, B2, C2, and D2 may together form a 6- to 10-membered carbocyclic ring or a 6- to 10-membered heterocyclic ring optionally containing one or more oxygen, nitrogen, or sulfur atom; a4 and b4 are independently from 0 to 3; R1 to R4, and R45 to R57 are independently selected from the group consisting of hydrogen, C1-C10 alkyl, C5-C12 aryl, C1-C10 alkoxyl, C1-C10 polyhydroxyalkyl, C5-C12 polyhydroxyaryl, C1-C10 aminoalkyl, mono- or oligosaccharide, peptide with 2 to 30 amino acid units, —CH2(CH2OCH2)b—CH2—OH, —(CH2)a—CO2H, —(CH2)a—CONH-Bm, —CH2—(CH2OCH2)b—CH2—CONH-Bm, —(CH2)a—NHCO-Bm, —CH2—(CH2OCH2)b—CH2—NHCO-Bm, —(CH2)a—OH and —CH2—(CH2OCH2)b—CO2H; Bm and Dm are independently selected from the group consisting of a bioactive peptide containing 2 to 30 amino acid units, an antibody, a mono- or oligosaccharide, a glycopeptide, a metal chelating agent, a radioactive or nonradioactive metal complex, and an echogenic agent; a and c are independently from 1 to 10; and b and d are independently from 1 to 30.
- 8. The composition of claim 6 wherein each of W4 and X4 is C(CH3)2; Y4 is —(CH2)2—CONH-Bm; Z4 is —(CH2)2-CONH-Dm; A2 is a single bond; A2, B2, C2, and D2 together form a 6-membered carbocyclic ring; a4 and b4 are independently galactose; each of R46 to R57 is hydrogen; Bm is Octreotate; and Dm is bombesin (7-14).
- 9. The composition of claim 6 further comprising one to ten groups containing Bm, Dm, and combinations thereof wherein W4 and X4 additionally include CR1R2.
- 10. The composition of claim 6 wherein Bm, Dm, and combinations thereof further comprise a porphyrin or a photodynamic therapy agent.
- 11. The composition of claim 6 further comprising a non-optical contrast agent.
- 12. The composition of claim 6 wherein the agent is formulated as at least one of a liposome, a micelle, a microcapsule, or a microparticle.
- 13. The composition of claim 6 wherein the agent is formulated in a long-lived liposome.
- 14. A composition comprising indocyanine dye of Formula
- 15. A method of performing a diagnostic or therapeutic procedure comprising administering to an individual an effective amount of the composition of claim 14.
- 16. A method for performing a diagnostic or therapeutic procedure comprising
administering to an individual an effective amount of the compound of formula 9wherein W4 and X4 are independently selected from the group consisting of —O—, —NR3, and —S—; Y4 is selected from the group consisting of —(CH2)a—CONH-Bm, —CH2—(CH2OCH2)b—CH2—CONH-Bm, —(CH2)a—NHCO-Bm, —CH2—(CH2OCH2)b—CH2—NHCO-Bm, —(CH2)a—N(R3)—(CH2)b—CONH-Bm, (CH2)a—N(R3)—(CH2)c—NHCO-Bm, —(CH2)a—N(R3)—CH2—(CH2OCH2)b—CH2—CONH-Bm, —(CH2)a—N(R3)—CH2—(CH2OCH2)b—CH2—NHCO-Bm, —CH2—(CH2OCH2)b—CH2—N(R3)—(CH2)a—CONH-Bm, —CH2—(CH2OCH2)b—CH2—N(R3)—(CH2)a—NHCO-Bm, —CH2—(CH2OCH2)b—CH2—N(R3)—CH2—(CH2OCH2)d—CONH-Bm, —CH2—(CH2OCH2)b—CH2—N(R3)—CH2—(CH2OCH2)d—NHCO-Bm, —(CH2)a—NR3R4, and —CH2(CH2OCH2)b—CH2NR3R4; Z4 is selected from the group consisting of —(CH2)a—CONH-Dm, —CH2—(CH2OCH2)b—CH2—CONH-Dm, —(CH2)a—NHCO-Dm, —CH2—(CH2OCH2)b—CH2—NHCO-Dm, —(CH2)a—N(R3)—(CH2)b—CONH-Dm, (CH2)a—N(R3)—(CH2)c—NHCO-Dm, —(CH2)a—N(R3)—CH2—(CH2OCH2)b—CH2—CONH-Dm, —(CH2)a—N(R3)—CH2—(CH2OCH2)b—CH2—NHCO-Dm, —CH2—(CH2OCH2)b—CH2—N(R3)—(CH2)a—CONH-Dm, —CH2—(CH2OCH2)b—CH2—N(R3)—(CH2)a—NHCO-Dm, —CH2—(CH2OCH2)b—CH2—N(R3)—CH2—(CH2OCH2)d—CONH-Dm, —CH2—(CH2OCH2)b—CH2—N(R3)—CH2—(CH2OCH2)d—NHCO-Dm, —(CH2)a—NR3R4, and —CH2(CH2OCH2)b—CH2NR3R4; A2 is a single or a double bond; B2, C2, and D2 are independently selected from the group consisting of —O—, —S—, —Se—, —P—, —CR1R2, —CR1, alkyl, NR3, and —C═O; A2, B2, C2, and D2 may together form a 6- to 12-membered carbocyclic ring or a 6- to 12-membered heterocyclic ring optionally containing one or more oxygen, nitrogen, or sulfur atom; a4 and b4 are independently from 0 to 5; R1 to R4, and R45 to R57 are independently selected from the group consisting of hydrogen, C1-C10 alkyl, C5-C20 aryl, C1-C10 alkoxyl, C1-C10 polyalkoxyalkyl, C1-C20 polyhydroxyalkyl, C5-C20 polyhydroxyaryl, C1-C10 aminoalkyl, glucose derivatives of R groups, cyano, nitro, halogen, saccharide, peptide, —CH2(CH2OCH2)b—CH2—OH, —(CH2)a—CO2H, —(CH2)a—CONH-Bm, —CH2—(CH2OCH2)b—CH2—CONH-Bm, —(CH2)a—NHCO-Bm, —CH2—(CH2OCH2)b—CH2—NHCO-Bm, —(CH2)a—OH and —CH2—(CH2OCH2)b—CO2H; Bm and Dm are independently selected from the group consisting of a bioactive peptide, a protein, a cell, an antibody, an antibody fragment, a saccharide, a glycopeptide, a peptidomimetic, a drug, a drug mimic, a hormone, a metal chelating agent, a radioactive or nonradioactive metal complex, and an echogenic agent; a and c are independently from 1 to 20; and b and d are independently from 1 to 100, and performing the diagnostic or therapeutic procedure.
- 17. The method of claim 16 comprising administering to an individual an effective amount of the compound wherein W4 and X4 are independently selected from the group consisting of —NR3 and —S—; Y4 is selected from the group consisting of —(CH2)a—CONH-Bm, —CH2—(CH2OCH2)b—CH2—CONH-Bm, —(CH2)a—NHCO-Bm, —CH2—(CH2OCH2)b—CH2—NHCO-Bm, —(CH2)a—NR3R4, and —CH2(CH2OCH2)b—CH2NR3R4; Z4 is selected from the group consisting of —(CH2)a—CONH-Dm, —CH2—(CH2OCH2)b—CH2—CONH-Dm, —(CH2)a—NHCO-Dm, —CH2—(CH2OCH2)b—CH2—NHCO-Dm, —(CH2)a—NR3R4, and —CH2(CH2OCH2)b—CH2NR3R4; A2 is a single or a double bond; B2, C2, and D2 are independently selected from the group consisting of —O—, —S—, NR3, (CH2)a—CR1R2, and —CR1; A2, B2, C2, and D2 may together form a 6- to 10-membered carbocyclic ring or a 6- to 10-membered heterocyclic ring optionally containing one or more oxygen, nitrogen, or sulfur atom; a4 and b4 are independently from 0 to 3; R1 to R4, and R45 to R57 are independently selected from the group consisting of hydrogen, C1-C10 alkyl, C5-C12 aryl, C1-C10 alkoxyl, C1-C10 polyhydroxyalkyl, C5-C12 polyhydroxyaryl, C1-C10 aminoalkyl, mono- or oligosaccharide, peptide with 2 to 30 amino acid units, —CH2(CH2OCH2)b—CH2—OH, —(CH2)a—CO2H, —(CH2)a—CONH-Bm, —CH2—(CH2OCH2)b—CH2—CONH-Bm, —(CH2)a—NHCO-Bm, —CH2—(CH2OCH2)b—CH2—NHCO-Bm, —(CH2)a—OH and —CH2—(CH2OCH2)b—CO2H; Bm and Dm are independently selected from the group consisting of a bioactive peptide containing 2 to 30 amino acid units, an antibody, a mono- or oligosaccharide, a glycopeptide, a metal chelating agent, a radioactive or nonradioactive metal complex, and an echogenic agent; a and c are independently from 1 to 10; and b and d are independently from 1 to 30.
- 18. The method of claim 17 comprising administering to an individual an effective amount of the compound wherein each of W4 and X4 is C(CH3)2; Y4 is —(CH2)2—CONH-Bm; Z4 is —(CH2)2—CONH-Dm; A2 is a single bond; A2, B2, C2, and D2 together form a 6-membered carbocyclic ring; each a4 and b4 is 1; R45 is galactose; each R46 to R57 is hydrogen; Bm is Octreotate; Dm is bombesin (7-14).
- 19. The method of claim 16 wherein said procedure utilizes light of wavelength in the region of 350-1300 nm.
- 20. The method of claim 16 wherein the diagnostic procedure is at least one of optical tomography and fluorescence endoscopy.
- 21. The method of claim 16 further comprising monitoring a blood clearance profile of said compound by a method selected from the group consisting of fluorescence, absorbance, and light scattering, wherein light of wavelength in the region of 350-1300 nm is used.
- 22. The method of claim 16 wherein said procedure further comprises imaging and therapy, wherein said imaging and therapy is selected from the group consisting of absorption, light scattering, photoacoustic and sonofluoresence technique.
- 23. The method of claim 16 wherein said procedure is capable of diagnosing atherosclerotic plaques and blood clots.
- 24. The method of claim 16 wherein said procedure comprises administering localized therapy.
- 25. The method of claim 16 wherein said therapeutic procedure comprises photodynamic therapy.
- 26. The method of claim 16 wherein said therapeutic procedure comprises laser assisted guided surgery for the detection of micrometastases.
- 27. The method of claim 16 further comprising adding a biocompatible organic solvent at a concentration of one to fifty percent of the compound to prevent in vivo or in vitro fluorescence quenching.
- 28. The method of claim 27 wherein said compound is dissolved in a medium comprising one to fifty percent dimethyl sulfoxide.
- 29. The method of claim 16 wherein the compound comprises one to ten groups containing Bm, Dm, and combinations thereof wherein W4 and X4 additionally include CR1R2 providing a cooperative effect to enhance binding of the compound.
- 30. The method of claim 29 further comprising attaching a compound selected from the group consisting of a porphyrin and a photodynamic therapy agent to Bm, Dm, and combinations thereof, and providing light of a wavelength sufficient to activate the porphyrin or phototherapy agent.
- 31. The method of claim 29 wherein the procedure monitors blood clearance of the compound to detect an abnormality.
- 32. The method of claim 29 further comprising activating the compound prior to performing the procedure.
- 33. The method of claim 16 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, and single photon emission computed tomography.
- 34. The method of claim 16 wherein the compound administered has at least one R group replaced by EDTA, DPTA, or DOTA.
- 35. The method of claim 34 wherein the compound administered further comprises a radioactive metal ion or a paramagnetic metal ion.
- 36. The method of claim 35 further comprising imaging by at least one of optical imaging and magnetic resonance imaging.
- 37. The method of claim 16 wherein the compound is administered in a formulation selected from at least one of liposomes, micelles, microcapsules, or microparticles.
- 38. A method of imaging a patient comprising administering a non-optical contrast agent composition further comprising the compound of claim 1 and performing at least one of an optical imaging procedure or a non-optical imaging procedure.
- 39. The method of claim 38 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 compostion, a positron emission tomography composition, a single photon emission computed tomography composition, and an ultrasound composition.
- 40. The method of claim 38 wherein the compound stabilizes or buffers the non-optical contrast agent composition.
Parent Case Info
[0001] This application is a continuation-in-part of U.S. patent application Ser. No. 09/863,971 filed May 23, 2001, which is a continuation-in-part of application Ser. No. 09/484,320 filed Jan. 18, 2000, now U.S. Pat. No. 6,180,087, each of which are expressly incorporated by reference herein in its entirety.
Continuation in Parts (2)
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Number |
Date |
Country |
Parent |
09863971 |
May 2001 |
US |
Child |
10654033 |
Sep 2003 |
US |
Parent |
09484320 |
Jan 2000 |
US |
Child |
09863971 |
May 2001 |
US |