Detection and therapy of vulnerable plaque with fluorescent and/or radiolabeled compositions

• US 20060073100A1
• Filed: 08/09/2002
• Published: 04/06/2006
• Est. Priority Date: 06/04/2001
• Status: Abandoned Application

• Current Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Original Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Inventors: Hasan, Tayyaba, Elmaleh, David, Tawakol, Ahmed, Fischman, Alan, Anderson, Rox, Muller, James, Hamblin, Michael R., Gewirtz, Henry
• Application Number:
  US10/216,026
• Publication Number:
  US 20060073100A1
• Time in Patent Office: Days
• US Class Current: 424/9.600
• CPC Class Codes: A61B 18/20 using laser
• CPC Class Codes: A61B 18/245 for removing obstructions in blood vessels or calculi
• CPC Class Codes: A61B 2017/00057 Light
• CPC Class Codes: A61B 2017/00079 Radioactivity
• CPC Class Codes: A61B 2018/00904 Automatic detection of target tissue
• CPC Class Codes: A61B 5/0071 by measuring fluorescence emission
• CPC Class Codes: A61B 5/0075 by spectroscopy, i.e. measuring spectra, e.g. Raman spectroscopy, infrared absorption spectroscopy A61B5/0071 takes precedence
• CPC Class Codes: A61B 5/0084 for introduction into the body, e.g. by catheters A61B5/1459 takes precedence
• CPC Class Codes: A61B 5/0086 using infrared radiation
• CPC Class Codes: A61B 6/4258 for detecting non x-ray radiation, e.g. gamma radiation A61B6/037 takes precedence
• CPC Class Codes: A61K 41/0057 Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
• CPC Class Codes: A61K 41/0061 5-aminolevulinic acid-based PDT: 5-ALA-PDT involving porphyrins or precursors of protoporphyrins generated in vivo from 5-ALA
• CPC Class Codes: A61K 41/0071 PDT with porphyrins having exactly 20 ring atoms, i.e. based on the non-expanded tetrapyrrolic ring system, e.g. bacteriochlorin, chlorin-e6, or phthalocyanines
• CPC Class Codes: A61K 41/0076 PDT with expanded (metallo)porphyrins, i.e. having more than 20 ring atoms, e.g. texaphyrins, sapphyrins, hexaphyrins, pentaphyrins, porphocyanines
• CPC Class Codes: A61K 47/643 Albumins, e.g. HSA, BSA, ovalbumin or a Keyhole Limpet Hemocyanin [KHL]
• CPC Class Codes: A61K 51/0474 complexes or complex-forming compounds, i.e. wherein a radioactive metal (e.g. 111In3+) is complexed or chelated by, e.g. a N2S2, N3S, NS3, N4 chelating group
• CPC Class Codes: A61K 51/0491 Sugars, nucleosides, nucleotides, oligonucleotides, nucleic acids, e.g. DNA, RNA, nucleic acid aptamers
• CPC Class Codes: A61N 2005/0602 for treatment of blood vessels
• CPC Class Codes: A61N 5/0601 Apparatus for use inside the body
• CPC Class Codes: A61N 5/062 Photodynamic therapy, i.e. excitation of an agent
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 7/00 : Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system

Abstract

The present invention relates to methods for selectively targeting Photodynamic Therapy (“PDT”) to inflammatory components of vulnerable plaques. As such, the present invention provides methods for the identification of vulnerable plaques, using fluorescent compositions, which include photosensitizer compoisitions, and/or radiolabeled compounds, as well as methods to treat vulnerable plaques by selectively targeting and/or eliminating the inflammatory components of vulnerable plaques.

Claims

1. A method of stabilizing a vulnerable plaque in a subject comprising the steps of:

a) administering a therapeutically effective amount of at least one photosensitizer composition, wherein the photosensitizer composition is localized to the vulnerable plaque; and

b) light activating the photosensitizer composition to produce a phototoxic species; and

c) stabilizing the vulnerable plaque against rupture.

2. The method of claim 1, wherein the vulnerable plaque comprises inflammatory components, a large lipid pool, and a thin fibrous cap.

3. The method of claim 2, wherein the thin fibrous cap is less than about 150 microns thick.

4. The method of claim 2, wherein the thin fibrous cap is less than about 100 microns thick.

5. The method of claim 2, wherein inflammatory components are selected from the group consisting of inflammatory cells, lipids, procoagulants and agents that promote inhibition of extracellular matrix production or degradation of extracellular matrix.

6. The method of claim 5, wherein the inflammatory cells are selected from the group consisting of smooth muscle cells, leukocytes, lymphocytes, monocytes, macrophages, foam cells, mast cells, endothelial cells, platelets, erythrocytes and polymorphonuclear cells.

7. The method of claim 6, wherein the lymphocytes comprise B-lymphocytes and T-lymophocytes.

8. The method of claim 6, wherein the polymorphonuclear cells comprise granulocytes and neutrophils.

9. The method of claim 6, wherein the inflammatory cells comprise greater than about 10% macrophages and/or monocytes.

10. The method of claim 6, wherein the inflammatory cells comprises greater than about 25% macrophages and/or monocytes.

11. The method of claim 2, wherein the lipid content is greater than about 10%.

12. The method of claim 2, wherein the lipid content is greater than about 25%.

13. The method of claim 1, wherein the photosensitizer composition comprises a photosensitizer coupled to a molecular carrier.

14. The method of claim 13, wherein the molecular carrier targets inflammatory components selected from the group consisting of inflammatory cells, lipids, procoagulants and agents that promote inhibition of extracellular matrix production or degradation of extracellular matrix.

15. The method of claim 14, wherein the inflammatory cells are selected from the group consisting of smooth muscle cells, leukocytes, lymphocytes, monocytes, macrophages, foam cells, mast cells, endothelial cells, platelets, erythrocytes and polymorphonuclear cells.

16. The method of claim 15, wherein the lymphocytes comprise B-lymphocytes and T-lymophocytes.

17. The method of claim 15, wherein the polymorphonuclear cells comprise granulocytes and neutrophils.

18. The method of claim 13, wherein the molecular carrier is selected from the group consisting of serum proteins, receptor ligands, microspheres, liposomes, antibodies, growth factors, peptides, hormones and lipoproteins.

19. The method of claim 13, wherein the molecular carrier binds to a scavenger receptor.

20. The method of claim 19, wherein the molecular carrier is selected from the group consisting of maleylated albumin, daunorubicin, doxorubicin, oxidized low density lipoprotein, acetylated low density lipoprotein, oxidized high density lipoprotein, malondialdehyde treated proteins, formaldehyde treated albumin, glycated albumin, polyinosinic acid, glycated lipoproteins, dextran sulfate, anionic phospholipids, fucoidin, carrageenan, polyvinyl sulfate and monoclonal antibodies that recognize CD11b, CD11c, CD13, CD14, CD16a, CD32 or CD68.

21. The method of claim 20, wherein the anionic phospholipid is phosphatidyl serine.

22. The method of claim 13, where in the molecular carrier targets the photosensitizer composition to a T cell.

23. The method of claim 22, where in the molecular carrier is selected from the group consisting of monoclonal antibodies that recognize CD1, CD2, CD3, CD4, CD5, CD6, CD7, CD8, CD25, CD28, CD44 and CD71 and transferrin.

24. The method of claim 13, where in the molecular carrier targets the photosensitizer composition to the lipids comprising the lipid pool of the atheroma.

25. The method of claim 24, wherein the molecular carrier comprises a hydrophobic vehicles selected from the group consisting of liposomes, cremaphor EL, PEG/solvent mixtures, iodized castor oil, nanoparticles and micellar preparations.

26. The method of claim 25, wherein the liposomes contain cholesterol.

27. The method of claim 25, wherein the liposomes contain cardiolipin.

28. The method of claim 13, wherein the molecular carrier targets the photosensitizer composition to macrophages.

29. The method of claim 28, wherein the molecular carrier targets the photosensitizer composition to a macrophage biomolecule selected from the group consisting of For-Met-Leu-Phe, tenascin C, tissue factor, tissue inhibitor of MMP 1, tissue inhibitor of MMP 2, oxidized LDL receptor, heme oxygenase-1, human cartilage gp-39, IL-6, IL-6 receptor, IL-10, IL-10 receptor, lectin-like oxidized LDL-receptor, monocyte inflammatory protein-1, monocyte inflammatory protein-1 receptor and macrophage chemoattractant protein-1 receptor.

30. The method of claim 22, wherein the molecular carrier targets the photosensitizer composition to a T cell biomolecule selected from the group consisting of IL-10, IL-10 receptor, monocyte inflammatory protein-1, monocyte inflammatory protein-1 receptor and transferrin.

31. The method of claim 13, wherein the molecular carrier targets the photosensitizer composition to foam cells.

32. The method of claim 13, wherein the molecular carrier that targets the photosensitizer composition is a protease that degrades extracellular matrix.

33. The method of claim 32, wherein the protease is a metalloproteinase.

34. The method of claim 32, wherein the molecular carrier is a monoclonal antibody that binds to an epitope on a protease.

35. The method of claim 1, wherein the light activating the photosensitizer composition to produce a phototoxic species is administered in an amount sufficient to induce apoptosis and not necrosis of the cells comprising the vulnerable plaque.

53. The method of claim 1, wherein the photosensitizer is chlorin_e6.

54. The method of claim 53, wherein the light is administered in a 20-500 J/cm dose.

55. The method of claim 53, wherein the light is administered in a 50-300 J/cm dose.

56. The method of claim 53, wherein the light is administered in a 100-200 J/cm dose.

36. A method of stabilizing a vulnerable plaque in a subject comprising the steps of:

a) administering a therapeutically effective amount of at least one photosensitizer composition comprising a photosensitizer coupled to a molecular carrier; and

b) localizing the photosensitizer composition to a vulnerable plaque consisting of inflammatory components, a large lipid pool, and a thin fibrous cap that is less than about 150 microns thick; and

b) light activating the photosensitizer composition to produce a phototoxic species; and

c) stabilizing the vulnerable plaque against rupture.

37. The method of claim 36, wherein the wherein the light activating the photosensitizer composition to produce a phototoxic species is administered in an amount sufficient to induce apoptosis and not necrosis of the cells comprising the vulnerable plaque.

57. The method of claim 36, wherein the photosensitizer is chlorin_e6

58. The method of claim 57, wherein the light is administered in a 20-500 J/cm dose.

59. The method of claim 57, wherein the light is administered in a 50-300 J/cm dose.

60. The method of claim 57, wherein the light is administered in a 100-200 J/cm dose.

38. A method of stabilizing a vulnerable plaque in a subject comprising the steps of:

a) administering a therapeutically effective amount of at least one photosensitizer composition comprising a photosensitizer coupled to a molecular carrier; and

b) localizing the photosensitizer composition to a vulnerable plaque consisting of inflammatory components, a large lipid pool, and a thin fibrous cap that is less than about 150 microns thick; and

c) light activating the photosensitizer composition to produce a phototoxic species, and wherein the light further produces cross links in the fibrous cap; and

d) stabilizing the vulnerable plaque against rupture.

39. The method of claim 38, wherein the wherein the light activating the photosensitizer composition to produce a phototoxic species is administered in an amount sufficient to induce apoptosis and not necrosis of the cells comprising the vulnerable plaque.

61. The method of claim 38, wherein the photosensitizer is chlorin_e6

62. The method of claim 61, wherein the light is administered in a 20-500 J/cm dose.

63. The method of claim 61, wherein the light is administered in a 50-300 J/cm dose.

64. The method of claim 61, wherein the light is administered in a 100-200 J/cm dose.

40. A method of detecting a vulnerable plaque in a subject comprising the steps of:

a) administering a fluorescent composition; and

b) localizing the composition to the vulnerable plaque; and

c) light activating the composition to illuminate the vulnerable plaque; and

d) identifying the vulnerable plaque.

41. The method of claim 40, wherein the fluorescent composition comprises a photosensitizer coupled to a coupled to a molecular carrier.

42. The method of claim 40, wherein the fluorescent composition comprises a fluorescent dye coupled to a molecular carrier.

43. The method of claim 40, wherein the fluorescent composition comprises a photoactive dye coupled to a molecular carrier.

49. The method of claim 41, further comprising the steps of:

e) light activating the photosensitizer at the site of the vulnerable plaque to produce a phototoxic species; and

f) stabilizing the vulnerable plaque against rupture.

50. The method of claim 43, further comprising the steps of:

e) light activating the photoactive dye at the site of the vulnerable plaque to produce a phototoxic species; and

f) stabilizing the vulnerable plaque against rupture.

69. The method of claim 49, wherein the photosensitizer is chlorin_e6

70. The method of claim 69, wherein the light activating the photosensitizer is administered in a 20-500 J/cm dose.

71. The method of claim 69, wherein the light activating the photosensitizer is administered in a 50-300 J/cm dose.

72. The method of claim 69, wherein the light activating the photosensitizer is administered in a 100-200 J/cm dose.

73. The method of claim 50, wherein the photoactive dye is chlorin_e6.

74. The method of claim 73, wherein the light activating the photoactive dye is administered in a 20-500 J/cm dose.

75. The method of claim 73, wherein the light activating the photoactive dye is administered in a 50-300 J/cm dose.

76. The method of claim 73, wherein the light activating the photoactive dye is administered in a 100-200 J/cm dose.

85. The method of claim 41, wherein the photosensitizer is chlorin_e6

86. The method of claim 85, wherein the light is administered in a dose that is less than about 10 J/cm.

87. The method of claim 85, wherein the light is administered in a dose that is less than about 5 J/cm.

88. The method of claim 85, wherein the light is administered in a dose that is less than about 1 J/cm.

89. The method of claim 43, wherein the photoactive dye is chlorin_e6

90. The method of claim 89, wherein the light is administered in a dose that is less than about 10 J/cm.

91. The method of claim 89, wherein the light is administered in a dose that is less than about 5 J/cm.

92. The method of claim 89, wherein the light is administered in a dose that is less than about 1 J/cm.

44. A method of detecting a vulnerable plaque in a subject comprising the steps of:

a) administering a detectable amount of at least one fluorescent composition, wherein the fluorescent composition is localized to a vulnerable plaque; and

b) light activating the vulnerable plaque to produce a fluorescent species; and

c) identifying the vulnerable plaque.

45. The method of claim 44, wherein the fluorescent composition comprises a photosensitizer coupled to a coupled to a molecular carrier.

46. The method of claim 44, wherein the fluorescent composition comprises a fluorescent dye coupled to a molecular carrier.

47. The method of claim 44, wherein the fluorescent composition comprises a photoactive dye coupled to a molecular carrier.

51. The method of claim 45, further comprising the steps of:

d) light activating the photosensitizer at the site of the vulnerable plaque to produce a phototoxic species; and

e) stabilizing the vulnerable plaque against rupture.

52. The method of claim 47, further comprising the steps of:

d) light activating the photoactive dye at the site of the vulnerable plaque to produce a phototoxic species; and

e) stabilizing the vulnerable plaque against rupture.

77. The method of claim 51, wherein the photosensitizer is chlorin_e6.

78. The method of claim 77, wherein the light activating the photosensitizer is administered in a 20-500 J/cm dose.

79. The method of claim 77, wherein the light activating the photosensitizer is administered in a 50-300 J/cm dose.

80. The method of claim 77, wherein the light activating the photosensitizer is administered in a 100-200 J/cm dose.

81. The method of claim 52, wherein the photoactive dye is chlorin_e6

82. The method of claim 81, wherein the light activating the photoactive dye is administered in a 20-500 J/cm dose.

83. The method of claim 81, wherein the light activating the photoactive dye is administered in a 50-300 J/cm dose.

84. The method of claim 81, wherein the light activating the photosensitizer composition is administered in a 100-200 J/cm dose.

93. The method of claim 45, wherein the photosensitizer is chlorin_e6

94. The method of claim 93, wherein the light is administered in a dose that is less than about 10 J/cm.

95. The method of claim 93, wherein the light is administered in a dose that is less than about 5 J/cm.

96. The method of claim 93, wherein the light is administered in a dose that is less than about 1 J/cm.

97. The method of claim 47, wherein the photoactive dye is chlorin_e6

98. The method of claim 97, wherein the light is administered in a dose that is less than about 10 J/cm.

99. The method of claim 97, wherein the light is administered in a dose that is less than about 5 J/cm.

100. The method of claim 97, wherein the light is administered in a dose that is less than about 1 J/cm.

48. A method of detecting and treating a vulnerable plaque in a subject comprising the steps of:

a) administering a detectable amount of at least one fluorescent composition, wherein the fluorescent composition is localized to a vulnerable plaque; and

b) administering a therapeutically effective amount of at least one photosensitizer composition, wherein the photosensitizer composition is localized to a vulnerable plaque; and

c) light activating the vulnerable plaque to produce a fluorescent species; and

d) identifying the vulnerable plaque; and

e) light activating the photosensitizer composition at the site of the vulnerable plaque to produce a phototoxic species; and

f) stabilizing the vulnerable plaque against rupture.

65. The method of claim 48, wherein the photosensitizer composition comprises chlorin_e6.

66. The method of claim 65, wherein the light activating the photosensitizer composition is administered in a 20-500 J/cm dose.

67. The method of claim 65, wherein the light activating the photosensitizer composition is administered in a 50-300 J/cm dose.

68. The method of claim 65, wherein the light activating the photosensitizer composition is administered in a 100-200 J/cm dose.

101. The method of claim 48, wherein the fluorescent composition comprises is chlorin_e6

102. The method of claim 101, wherein the light activating the fluorescent composition is administered in a dose that is less than about 10 J/cm.

103. The method of claim 101, wherein the light activating the fluorescent composition administered in a dose that is less than about 5 J/cm.

104. The method of claim 101, wherein the light activating the fluorescent composition is administered in a dose that is less than about 1 J/cm.

105. A method of detecting and treating a vulnerable plaque in a subject comprising the steps of:

a) administering a detectable amount of at least one fluorescent composition, wherein the fluorescent composition is localized to a vulnerable plaque; and

administering a therapeutically effective amount of at least one photosensitizer composition, wherein the photosensitizer composition is localized to a vulnerable plaque; and

b) light activating the vulnerable plaque to produce a fluorescent species; and

c) identifying the vulnerable plaque; and

d) light activating the photosensitizer composition at the site of the vulnerable plaque to produce a phototoxic species;

e) and stabilizing the vulnerable plaque against rupture.

106. A method of detecting and treating a vulnerable plaque in a subject comprising the steps of:

a) administering a composition comprising a radiolabeled a molecular carrier; and

b) localizing the composition to the vulnerable plaque; and

c) measuring radioactive signal; and

d) identifying the vulnerable plaque; and

e) administering a therapeutically effective amount of at least one photosensitizer composition, wherein the photosensitizer composition is localized to the vulnerable plaque; and

f) light activating the photosensitizer composition at the site of the vulnerable plaque to produce a phototoxic species; and

g) stabilizing the vulnerable plaque against rupture.

107. A method of detecting a vulnerable plaque in a subject comprising the steps of:

a) administering a radiolabeled composition;

b) localizing the composition to the vulnerable plaque;

c) detecting a signal from the radiolabeled composition;

d) identifying the vulnerable plaque.

108. The method of claim 107, wherein the vulnerable plaque comprises inflammatory components, a large lipid pool, and a thin fibrous cap.

109. The method of claim 108, wherein the thin fibrous cap is less than about 150 microns thick.

110. The method of claim 108, wherein the thin fibrous cap is less than about 100 microns thick.

111. The method of claim 108, wherein inflammatory components are selected from the group consisting of inflammatory cells, lipids, procoagulants and agents that promote inhibition of extracellular matrix production or degradation of extracellular matrix.

112. The method of claim 111, wherein the inflammatory cells are selected from the group consisting of smooth muscle cells, leukocytes, lymphocytes, monocytes, macrophages, foam cells, mast cells, endothelial cells, platelets, erythrocytes and polymorphonuclear cells.

113. The method of claim 112, wherein the lymphocytes comprise B-lymphocytes and T-lymophocytes.

114. The method of claim 112, wherein the polymorphonuclear cells comprise granulocytes and neutrophils.

115. The method of claim 112, wherein the inflammatory cells comprise greater than about 10% macrophages and/or monocytes.

116. The method of claim 112, wherein the inflammatory cells comprises greater than about 25% macrophages and/or monocytes.

117. The method of claim 108, wherein the lipid content is greater than about 10%.

118. The method of claim 108, wherein the lipid content is greater than about 25%.

119. The method of claim 107, wherein the radiolabeled composition comprises a radioactive agent coupled to a molecular carrier.

120. The method of claim 119, wherein the molecular carrier targets inflammatory components selected from the group consisting of inflammatory cells, lipids, procoagulants and agents that promote inhibition of extracellular matrix production or degradation of extracellular matrix.

121. The method of claim 120, wherein the inflammatory cells are selected from the group consisting of smooth muscle cells, leukocytes, lymphocytes, monocytes, macrophages, foam cells, mast cells, endothelial cells, platelets, erythrocytes and polymorphonuclear cells.

122. The method of claim 121, wherein the lymphocytes comprise B-lymphocytes and T-lymophocytes.

123. The method of claim 121, wherein the polymorphonuclear cells comprise granulocytes and neutrophils.

124. The method of claim 119, wherein the molecular carrier is selected from the group consisting of serum proteins, receptor ligands, microspheres, liposomes, antibodies, growth factors, peptides, hormones and lipoproteins.

125. The method of claim 119, wherein the molecular carrier binds to a scavenger receptor.

126. The method of claim 125, wherein the molecular carrier is selected from the group consisting of maleylated albumin, daunorubicin, doxorubicin, oxidized low density lipoprotein, acetylated low density lipoprotein, oxidized high density lipoprotein, malondialdehyde treated proteins, formaldehyde treated albumin, glycated albumin, polyinosinic acid, glycated lipoproteins, dextran sulfate, anionic phospholipids, fucoidin, carrageenan, polyvinyl sulfate and monoclonal antibodies that recognize CD11b, CD11c, CD13, CD14, CD16a, CD32 or CD68.

127. The method of claim 126, wherein the anionic phospholipid is phosphatidyl serine.

128. The method of claim 119, where in the molecular carrier targets the radiolabeled composition to a T cell.

129. The method of claim 128, where in the molecular carrier is selected from the group consisting of monoclonal antibodies that recognize CD1, CD2, CD3, CD4, CD5, CD6, CD7, CD8, CD25, CD28, CD44 and CD71 and transferrin.

130. The method of claim 119, where in the molecular carrier targets the radiolabeled composition to lipids of the vulnerable plaque.

131. The method of claim 130, wherein the molecular carrier comprises a hydrophobic vehicles selected from the group consisting of liposomes, cremaphor EL, PEG/solvent mixtures, iodized castor oil, nanoparticles and micellar preparations.

132. The method of claim 131, wherein the liposomes contain cholesterol.

133. The method of claim 131, wherein the liposomes contain cardiolipin.

134. The method of claim 119, wherein the molecular carrier targets the radiolabeled composition to macrophages.

135. The method of claim 134, wherein the molecular carrier targets the radiolabeled composition to a macrophage biomolecule selected from the group consisting of tenascin C, tissue factor, tissue inhibitor of MMP 1, tissue inhibitor of MMP 2, oxidized LDL receptor, heme oxygenase-1, human cartilage gp-39, IL-6, IL-6 receptor, IL-10, IL-10 receptor, lectin-like oxidized LDL-receptor, monocyte inflammatory protein-1, monocyte inflammatory protein-1 receptor and macrophage chemoattractant protein-1 receptor.

136. The method of claim 128, wherein the molecular carrier targets the radiolabeled composition to a T cell biomolecule selected from the group consisting of IL-10, IL-10 receptor, monocyte inflammatory protein-1, monocyte inflammatory protein-1 receptor and transferrin.

137. The method of claim 119, wherein the molecular carrier targets the radiolabeled composition to foam cells.

138. The method of claim 119, wherein the molecular carrier that targets the radiolabeled composition a protease that degrades extracellular matrix.

139. The method of claim 138, wherein the protease is a metalloproteinase.

140. The method of claim 138, wherein the molecular carrier is a monoclonal antibody that binds to an epitope on a protease.

141. A method of detecting a vulnerable plaque in a subject comprising the steps of:

a) administering a detectable amount of at least one radiolabeled composition, wherein the radiolabeled composition is localized to a vulnerable plaque;

b) detecting a signal from the radiolabeled composition; and

c) identifying the vulnerable plaque.

142. A method of detecting and treating a vulnerable plaque in a subject comprising the steps of:

a) administering a detectable amount of at least one radiolabeled composition, wherein the radiolabeled composition is localized to a vulnerable plaque;

b) administering a therapeutically effective amount of at least one photosensitizer composition, wherein the photosensitizer composition is localized to a vulnerable plaque;

c) detecting a signal from the radiolabeled composition; and

d) identifying the vulnerable plaque;

e) light activating the photosensitizer composition at the site of the vulnerable plaque to produce a phototoxic species;

f) stabilizing the vulnerable plaque against rupture.

143. The method of claim 142, wherein the photosensitizer is chlorin_e6.

144. The method of claim 143, wherein the light is administered in a 20-500 J/cm dose.

145. The method of claim 143, wherein the light is administered in a 50-300 J/cm dose.

146. The method of claim 143, wherein the light is administered in a 100-200 J/cm dose.

147. A method of detecting and treating a vulnerable plaque in a subject comprising the steps of:

a) administering a composition comprising a radioactive agent and a photosensitizer coupled to a molecular carrier;

b) localizing the composition to the vulnerable plaque;

c) detecting a signal from the radiolabeled composition;

d) identifying the vulnerable plaque;

e) light activating the photosensitizer at the site of the vulnerable plaque to produce a phototoxic species; and

f) stabilizing the vulnerable plaque against rupture.

148. In yet another embodiment, a method of detecting and treating a vulnerable plaque in a subject comprising the steps of:

a) administering a radiolabeled composition wherein the radiolabeled composition is localized to a vulnerable plaque;

b) first detecting a signal from the radiolabeled composition; and

identifying the vulnerable plaque;

c) administering a therapeutically effective amount of at least one photosensitizer composition, wherein the photosensitizer composition is localized to the vulnerable plaque;

d) second light activating the photosensitizer composition at the site of the vulnerable plaque to produce a phototoxic species; and

e) stabilizing the vulnerable plaque against rupture.