Claims
- 1. A method for performing a diagnostic or therapeutic procedure comprising
administering to an individual an effective amount of the compound of formula 45wherein W6 and X6 are independently selected from the group consisting of —CR1R2, —O—, —NR3, and —S—; Y6 is 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, —H2(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—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; Z6 is 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, —CH2(CH2OCH2)b—CH2—OH, —(CH2)a—CO2H, —(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; A4 is a single or a double bond; B4, C4, and D4 are independently selected from the group consisting of —O—, —S—, —Se—, —P—, —CR1R2, —CR1, alkyl, NR3, and —C═O; A4, B4, C4, and D4 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; a6 is from 0 to 5; R′ to R4, and R67 to R79 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—(C H2OCH2)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 a 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, with the proviso that either Y6 or Z6 contains a biomolecule Bm or Dm, and with the proviso that when W6 and X6 are C((CH2)OH)2, Y6 is not (CH2)2—CONH-Bm, activating the compound, and performing the diagnostic or therapeutic procedure.
- 2. The method of claim 1 comprising administering to an individual an effective amount of the compound wherein W6 and X6 are independently selected from the group consisting of —C(CH3)2, —C((CH2)aOH)CH3, —C((CH2)aOH)2, —C((CH2)aCO2H)CH3, —C((CH2)aCO2H)2, —C((CH2)aNH2)CH3, C((CH2)aNH2)2, C((CH2)aNR3R4)2, —NR3, and —S—; Y6 is 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, —CH2(CH2OCH2)b—CH2—OH, —(CH2)a—CO2H, —(CH2)a—CONH-Bm, —CH2—(CH2OCH2)b—CH2—CONH-Bm, —(CH2)a—NHCO-Bm, —CH2—(CH2° C. H2)b—CH2—NHCO-Bm, —(CH2)a—NR3R4, and —CH2(CH2OCH2)b—CH2NR3R4; Z6 is 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, —CH2(CH2OCH2)b—CH2—OH, —(CH2)a—CO2H, —(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; A4 is a single or a double bond; B4, C4, and D4 are independently selected from the group consisting of —O—, —S—, NR3, (CH2)a—CR1R2, and —CR1; A4, B4, C4, and D4 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; a6 is from 0 to 3; R1 to R4, and R67 to R79 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, with the proviso that either Y6 or Z6 contains a biomolecule Bm or Dm.
- 3. The method of claim 2 comprising administering to an individual an effective amount of the compound wherein each of W6 and X6 is C((CH2)OH)2; Y6 is —(CH2)2—CONH-Bm; Z6 is —(CH2)2—CO2H; A4 is a single bond; A4, B4, C4, and D4 together form a 6-membered carbocyclic ring; a6 is 1; R67 is galactose; each R68 to R79 is hydrogen; and Bm is Octreotate.
- 4. The method of claim 1 wherein said procedure utilizes light of wavelength in the region of 350-1300 nm.
- 5. The method of claim 1 wherein the diagnostic procedure is optical tomography.
- 6. The method of claim 1 wherein said diagnostic procedure is fluorescence endoscopy.
- 7. The method of claim 1 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.
- 8. The method of claim 1 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.
- 9. The method of claim 1 wherein said procedure is capable of diagnosing atherosclerotic plaques and blood clots.
- 10. The method of claim 1 wherein said procedure comprises administering localized therapy.
- 11. The method of claim 1 wherein said therapeutic procedure comprises photodynamic therapy.
- 12. The method of claim 1 wherein said therapeutic procedure comprises laser assisted guided surgery for the detection of micrometastases.
- 13. The method of claim 1 further comprising adding a biocompatible organic solvent at a concentration of one to fifty percent to the compound to prevent in vivo or in vitro fluorescence quenching.
- 14. The method of claim 13 wherein said compound is dissolved in a medium comprising one to fifty percent of at least one of dimethyl sulfoxide, ethyl alcohol, isopropyl alcohol, or glycerol.
- 15. The method of claim 1 wherein the compound comprises one to ten groups containing Bm, Dm, and combinations thereof providing a cooperative effect to enhance binding of the compound.
- 16. The method of claim 15 further comprising attaching a compound selected from the group consisting of a porphyrin and a photodynamic therapy agent to biomolecule Bm or Dm, and providing light of a wavelength sufficient to activate the porphyrin or phototherapy agent.
- 17. The method of claim 15 wherein the procedure monitors blood clearance of the compound to detect an abnormality.
- 18. The method of claim 15 further comprising activating the compound prior to performing the procedure.
- 19. The method of claim 1 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.
- 20. The method of claim 1 wherein the compound administered has at least one R group replaced by EDTA, DOTA, or DOTA.
- 21. The method of claim 20 wherein the compound administered further comprises a radioactive metal ion or a paramagnetic metal ion.
- 22. The method of claim 21 further comprising imaging by at least one of optical imaging or magnetic resonance imaging.
- 23. The method of claim 1 wherein the compound is administered in a formulation selected from at least one of liposomes, micelles, microcapsules, or microparticles.
- 24. 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.
- 25. The method of claim 24 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, or an ultrasound composition.
- 26. The method of claim 25 wherein the compound stablilizes or buffers the non-optical contrast agent composition.
- 27. A method to reduce aggregation of a dye administerable to a patient for a photodiagnostic or phototherapeutic procedure comprising adding to the dye a biocompatible organic solvent at a concentration ranging from about 1% to about 50% to reduce dye aggregation.
- 28. The method of claim 27 wherein the biocompatible organic solvent is added to a pharmaceutically acceptable formulation of the dye.
- 29. The method of claim 27 wherein the dye is dissolved or suspended in the biocompatible organic solvent.
- 30. The method of claim 27 where the biocompatible organic solvent is selected from the group consisting of dimethylsulfoxide, ethyl alcohol, isopropyl alcohol, glycerol, a polyol, or combinations thereof.
- 31. The method of claim 27 wherein the dye is represented by formulas 1, 2, 3, or 4.
- 32. A method to enhance fluorescence of a dye administerable to a patient for a photodiagnostic or phototherapeutic procedure comprising adding to the dye a biocompatible organic solvent at a concentration ranging from about 1% to about 50% to enhance dye fluorescence.
- 33. The method of claim 32 wherein the biocompatible organic solvent is added to a pharmaceutically acceptable formulation of the dye.
- 34. The method of claim 32 wherein the dye is dissolved or suspended in the biocompatible organic solvent.
- 35. The method of claim 32 where the biocompatible organic solvent is selected from the group consisting of dimethylsulfoxide, ethyl alcohol, isopropyl alcohol, glycerol, a polyol, or combinations thereof.
- 36. The method of claim 32 wherein the dye is represented by formulas 1, 2, 3, or 4.
- 37. A method to maintain fluorescence of a dye in a photodiagnosis or phototherapy procedure comprising administering to an individual an effective amount of a composition comprising a biocompatible organic solvent at a concentration from about 1% to about 50% and a dye of formula 4
- 38. The method of claim 37 wherein the organic solvent is selected from the group consisting of dimethylsulfoxide, ethyl alcohol, isopropyl alcohol, a polyol, a glycerol, and combinations thereof.
- 39. A method to maintain fluorescence of a dye in a photodiagnosis or phototherapy procedure comprising administering to an individual an effective amount of a composition comprising a biocompatible organic solvent at a concentration from about 1% to about 50% and a dye of formula 1
- 40. The method of claim 39 wherein the organic solvent is selected from the group consisting of dimethylsulfoxide, ethyl alcohol, isopropyl alcohol, a polyol, a glycerol, and combinations thereof.
- 41. A method to maintain fluorescence of a dye in a photodiagnosis or phototherapy procedure comprising administering to an individual an effective amount of a composition comprising a biocompatible organic solvent at a concentration from about 1% to about 50% and a dye of formula 2
- 42. The method of claim 41 wherein the organic solvent is selected from the group consisting of dimethylsulfoxide, ethyl alcohol, isopropyl alcohol, a polyol, a glycerol, and combinations thereof.
- 43. A method to maintain fluorescence of a dye in a photodiagnosis or phototherapy procedure comprising administering to an individual an effective amount of a composition comprising a biocompatible organic solvent at a concentration from about 1% to about 50% and a dye of formula 3
- 44. The method of claim 43 wherein the organic solvent is selected from the group consisting of dimethylsulfoxide, ethyl alcohol, isopropyl alcohol, a polyol, a glycerol, and combinations thereof.
Parent Case Info
[0001] This application is a continuation-in-part of co-pending U.S. patent application Ser. No. 09/864,011 filed May 23, 2001, which is a continuation-in-part of U.S. Pat. No. 6,395,257, Ser. No. 09/484,322 filed Jan. 18, 2000, each of which is expressly incorporated by reference herein it is entirety.
Continuation in Parts (2)
|
Number |
Date |
Country |
Parent |
09864011 |
May 2001 |
US |
Child |
10800531 |
Mar 2004 |
US |
Parent |
09484322 |
Jan 2000 |
US |
Child |
09864011 |
May 2001 |
US |