Fluorinated photosensitizers related to chlorins and bacteriochlorins for photodynamic therapy

• US 20040044197A1
• Filed: 06/27/2003
• Published: 03/04/2004
• Est. Priority Date: 06/27/2002
• Status: Active Grant

• Current Assignee: Health Research Incorporated
• Original Assignee: Health Research Incorporated
• Inventors: Pandey, Ravindra K., Dougherty, Thomas J., Potter, William R.
• Granted Patent: US 7,166,719 B2
• Time in Patent Office: Days
• US Class Current: 540/140
• 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: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07D 471/22 in which the condensed systems contains four or more hetero rings
• CPC Class Codes: C09B 47/00 Porphines; Azaporphines non-dyeing compounds C07D487/22
• CPC Class Codes: C09B 69/108 containing a phthalocyanine dye

Abstract

Provided herein are compounds for detection, diagnosis and treatment of target tissues or target compositions, including hyperproliferative tissues such as tumors, using photodynamic methods. In particular, photosensitizer compounds that collect in hyperproliferative tissue are provided. In another embodiment, compounds that absorb light at a wavelength of from about 700 to about 850 nm are provided. In a further embodiment, compounds that are detectable by magnetic resonance imaging are provided.

Claims

1. A tetrapyrrole compound containing a fluorinated substituent, wherein the tetrapyrrole compound is a chlorin or bacteriochlorin.

2. The compound of claim 1 wherein the fluorinated substituent is a fluorinated phenyl, fluorinated heterocyclic or fluorinated alkyl group.

23. A pharmaceutical composition, comprising a compound of claim 1 or a pharmaceutically acceptable derivative thereof in a pharmaceutically acceptable carrier.

24. An article of manufacture, comprising packaging material and a compound of claim 1 or a pharmaceutically acceptable derivative of a compound of claim 1 contained within the packaging material, wherein the compound or salt thereof is effective in a photodynamic therapy treatment for ameliorating the symptoms of a hyperproliferative disorder;

and the packaging material includes a label that indicates that the compound or salt thereof is used in a photodynamic therapy treatment for ameliorating the symptoms of a hyperproliferative disorder.

25. The compound of claim 1 or a pharmaceutically acceptable derivative thereof when used for the treatment of hyperproliferative tissue.

26. The compound of claim 1 or a pharmaceutically acceptable derivative thereof when used to detect a hyperproliferative tissue.

27. The compound of claim 1 or a pharmaceutically acceptable derivative thereof when used in a photodynamic therapy.

28. The compound of claim 1 or a pharmaceutically acceptable derivative thereof when used to destroy a target composition within a subject.

29. Use of the compound of claim 1 or a pharmaceutically acceptable derivative thereof for formulation of a medicament for the treatment of hyperproliferative disorders.

30. A method for administering a therapy to a target, comprising:

(i) administering to a subject the compound of claim 1 or a pharmaceutically acceptable derivative thereof that preferentially associates with the target, and

(ii) irradiating the subject with light of a wavelength and total fluence sufficient to produce a therapeutic effect.

31. The method of claim 30, wherein the target is selected from the group consisting of:

a vascular endothelial tissue, a neovasculature tissue, a neovasculature tissue present in an eye, an abnormal vascular wall of a tumor, a solid tumor, a tumor of a head, a tumor of a neck, a tumor of an eye, a tumor of a gastrointestinal tract, a tumor of a liver, a tumor of a breast, a tumor of a prostate, a tumors of a lung, a nonsolid tumor, malignant cells of one of a hematopoietic tissue and a lymphoid tissue, lesions in a vascular system, a diseased bone marrow, and diseased cells in which the disease is one of an autoimmune and an inflammatory disease.

32. The method of claim 30, wherein the target composition is selected from the group consisting of bacteria, viruses, fungi, protozoa, and toxins.

33. The method of claim 30, further comprising the step of allowing sufficient time for any of the compound that is not preferentially associated to the target tissue to clear from non-target tissue of the subject prior to the step of irradiating.

34. The method of claim 30 wherein the compound is conjugated to a targeting agent.

35. The method of claim 34 wherein the targeting agent is one of an antibody or an antibody fragment that is specific in binding with the target tissue.

36. The method of claim 34 wherein the targeting agent is a peptide that is specific in binding with the target tissue.

37. The method of claim 34, wherein the targeting agent is a liposomal preparation.

38. A method of photodynamic therapy for treating hyperproliferative tissue in a subject, comprising:

(i) administering to the subject the compound of claim 1 or a pharmaceutically acceptable derivative thereof that preferentially associates with the hyperproliferative tissue, and

(ii) irradiating the subject with light of a wavelength and fluence sufficient to activate the compound, whereby the hyperproliferative tissue is destroyed or impaired.

39. A method for detecting the presence of a hyperproliferative tissue in a subject comprising:

(i) administering to the subject a sufficient quantity of the compound of claim 1 or a pharmaceutically acceptable derivative thereof that preferentially associates with the hyperproliferative tissue; and

(ii) visualizing the compound within the patient.

40. The method of claim 39 wherein the step of visualizing is accomplished by generating an MRI image of at least a part of the patient'"'"'s body.

41. The method of claim 39 wherein the step of visualizing is accomplished by exposing the conjugated compound with light of sufficient energy to cause the compound to fluoresce.

42. A method for detecting a target in a biological sample, comprising:

(i) adding to the biological sample the compound of claim 1 or a pharmaceutically acceptable derivative thereof that binds to the target; and

(ii) detecting the compound.

43. The method of claim 42, wherein the biological sample is selected from the group consisting of blood, urine, saliva, tears, synovial fluid, sweat, interstitial fluid, sperm, cerebrospinal fluid, ascites fluid, and/or tumor tissue biopsy and circulating tumor cells.

44. A method of diagnosing an infecting agent in a patient, comprising:

(i) conjugating to the compound of claim 1 or a pharmaceutically acceptable derivative thereof a targeting agent specific for the infecting agent, whereby a conjugated compound is formed;

(ii) administering to the patient the conjugated compound; and

(iii) visualizing the conjugated compound within the patient.

45. The method of claim 44 wherein the step of visualizing is accomplished by generating a MRI image of at least a part of the patient'"'"'s body.

46. The method of claim 44 wherein the step of visualizing is accomplished by exposing the conjugated compound with light of sufficient energy to cause the compound to fluoresce.

47. A method of generating an image of a target tissue or target composition in a subject, comprising:

(i) administering to the subject the compound of claim 1 or a pharmaceutically acceptable derivative thereof; and

(ii) generating an image of at least a part of the subject to which the compound has preferentially associated.

48. The method of claim 47 wherein the image is a nuclear imaging image.

49. A method of labeling a target tissue for diagnostic radiology, comprising:

(i) administering to a subject the compound of claim 1 or a pharmaceutically acceptable derivative thereof; and

(ii) allowing sufficient time for any compound that is not preferentially associated to the target tissue to clear from non-target tissue of the subject, whereby the target tissue can be distinguished from non-target tissue in an MRI image of the subject.

50. A method of providing a medical therapy to an animal, comprising:

(i) administering to the animal the compound of claim 1 or a pharmaceutically acceptable derivative thereof, and

(ii) irradiating the animal with light of a wavelength and fluence sufficient to activate the compound, whereby the hyperproliferative tissue is destroyed or impaired.

51. The compound of claim 1 or a pharmaceutically acceptable derivative thereof when used for the labeling of a target tissue for diagnostic radiology.

52. A kit to treat hyperproliferative disorders, comprising the compound of claim 1 or a pharmaceutically acceptable derivative thereof and instructions teaching a method of photodynamic therapy.

53. A kit to label specific tissues for diagnostic radiology, comprising the compound of claim 1 or a pharmaceutically acceptable derivative thereof and instructions teaching a method of magnetic resonance imaging.

54. A combination, comprising:

the compound of claim 1 or a pharmaceutically acceptable derivative thereof; and

a light source.

55. A combination, comprising:

the compound of claim 1 or pharmaceutically acceptable derivatives thereof; and

a magnetic resonance imaging device.

3. A compound of the formula:

4. The compound of claim 3 wherein R₉ is —

CH₂CH₂CO₂R_a, where R_a is hydrogen or lower alkyl of 1-8 carbons.

56. A pharmaceutical composition, comprising a compound of claim 3 or a pharmaceutically acceptable derivative thereof in a pharmaceutically acceptable carrier.

57. An article of manufacture, comprising packaging material and a compound of claim 3 or a pharmaceutically acceptable derivative of a compound of claim 3 contained within the packaging material, wherein the compound or salt thereof is effective in a photodynamic therapy treatment for ameliorating the symptoms of a hyperproliferative disorder;

and the packaging material includes a label that indicates that the compound or salt thereof is used in a photodynamic therapy treatment for ameliorating the symptoms of a hyperproliferative disorder.

58. The compound of claim 3 or a pharmaceutically acceptable derivative thereof when used for the treatment of hyperproliferative tissue.

59. The compound of claim 3 or a pharmaceutically acceptable derivative thereof when used to detect a hyperproliferative tissue.

60. The compound of claim 3 or a pharmaceutically acceptable derivative thereof when used in a photodynamic therapy.

61. The compound of claim 3 or a pharmaceutically acceptable derivative thereof when used to destroy a target composition within a subject.

62. Use of the compound of claim 3 or a pharmaceutically acceptable derivative thereof for formulation of a medicament for the treatment of hyperproliferative disorders.

63. A method for administering a therapy to a target, comprising:

(i) administering to a subject the compound of claim 3 or a pharmaceutically acceptable derivative thereof that preferentially associates with the target, and

(ii) irradiating the subject with light of a wavelength and total fluence sufficient to produce a therapeutic effect.

64. The method of claim 63, wherein the target is selected from the group consisting of:

a vascular endothelial tissue, a neovasculature tissue, a neovasculature tissue present in an eye, an abnormal vascular wall of a tumor, a solid tumor, a tumor of a head, a tumor of a neck, a tumor of an eye, a tumor of a gastrointestinal tract, a tumor of a liver, a tumor of a breast, a tumor of a prostate, a tumors of a lung, a nonsolid tumor, malignant cells of one of a hematopoietic tissue and a lymphoid tissue, lesions in a vascular system, a diseased bone marrow, and diseased cells in which the disease is one of an autoimmune and an inflammatory disease.

65. The method of claim 63, wherein the target composition is selected from the group consisting of bacteria, viruses, fungi, protozoa, and toxins.

66. The method of claim 63, further comprising the step of allowing sufficient time for any of the compound that is not preferentially associated to the target tissue to clear from non-target tissue of the subject prior to the step of irradiating.

67. The method of claim 63 wherein the compound is conjugated to a targeting agent.

68. The method of claim 67 wherein the targeting agent is one of an antibody or an antibody fragment that is specific in binding with the target tissue.

69. The method of claim 67 wherein the targeting agent is a peptide that is specific in binding with the target tissue.

70. The method of claim 67, wherein the targeting agent is a liposomal preparation.

71. A method of photodynamic therapy for treating hyperproliferative tissue in a subject, comprising:

(i) administering to the subject the compound of claim 3 or a pharmaceutically acceptable derivative thereof that preferentially associates with the hyperproliferative tissue, and

(ii) irradiating the subject with light of a wavelength and fluence sufficient to activate the compound, whereby the hyperproliferative tissue is destroyed or impaired.

72. A method for detecting the presence of a hyperproliferative tissue in a subject comprising:

(i) administering to the subject a sufficient quantity of the compound of claim 3 or a pharmaceutically acceptable derivative thereof that preferentially associates with the hyperproliferative tissue; and

(ii) visualizing the compound within the patient.

73. The method of claim 72 wherein the step of visualizing is accomplished by generating an MRI image of at least a part of the patient'"'"'s body.

74. The method of claim 72 wherein the step of visualizing is accomplished by exposing the conjugated compound with light of sufficient energy to cause the compound to fluoresce.

75. A method for detecting a target in a biological sample, comprising:

(i) adding to the biological sample the compound of claim 3 or a pharmaceutically acceptable derivative thereof that binds to the target; and

(ii) detecting the compound.

76. The method of claim 75, wherein the biological sample is selected from the group consisting of blood, urine, saliva, tears, synovial fluid, sweat, interstitial fluid, sperm, cerebrospinal fluid, ascites fluid, and/or tumor tissue biopsy and circulating tumor cells.

77. A method of diagnosing an infecting agent in a patient, comprising:

(i) conjugating to the compound of claim 3 or a pharmaceutically acceptable derivative thereof a targeting agent specific for the infecting agent, whereby a conjugated compound is formed;

(ii) administering to the patient the conjugated compound; and

(iii) visualizing the conjugated compound within the patient.

78. The method of claim 77 wherein the step of visualizing is accomplished by generating a MRI image of at least a part of the patient'"'"'s body.

79. The method of claim 77 wherein the step of visualizing is accomplished by exposing the conjugated compound with light of sufficient energy to cause the compound to fluoresce.

80. A method of generating an image of a target tissue or target composition in a subject, comprising:

(i) administering to the subject the compound of claim 3 or a pharmaceutically acceptable derivative thereof; and

(ii) generating an image of at least a part of the subject to which the compound has preferentially associated.

81. The method of claim 80 wherein the image is a nuclear imaging image.

82. A method of labeling a target tissue for diagnostic radiology, comprising:

(i) administering to a subject the compound of claim 3 or a pharmaceutically acceptable derivative thereof; and

(ii) allowing sufficient time for any compound that is not preferentially associated to the target tissue to clear from non-target tissue of the subject, whereby the target tissue can be distinguished from non-target tissue in an MRI image of the subject.

83. A method of providing a medical therapy to an animal, comprising:

(i) administering to the animal the compound of claim 3 or a pharmaceutically acceptable derivative thereof, and

(ii) irradiating the animal with light of a wavelength and fluence sufficient to activate the compound, whereby the hyperproliferative tissue is destroyed or impaired.

84. The compound of claim 3 or a pharmaceutically acceptable derivative thereof when used for the labeling of a target tissue for diagnostic radiology.

85. A kit to treat hyperproliferative disorders, comprising the compound of claim 3 or a pharmaceutically acceptable derivative thereof and instructions teaching a method of photodynamic therapy.

86. A kit to label specific tissues for diagnostic radiology, comprising the compound of claim 3 or a pharmaceutically acceptable derivative thereof and instructions teaching a method of magnetic resonance imaging.

87. A combination, comprising:

the compound of claim 3 or a pharmaceutically acceptable derivative thereof; and

a light source.

88. A combination, comprising:

the compound of claim 3 or pharmaceutically acceptable derivatives thereof; and

a magnetic resonance imaging device.

5. A compound of the formula:

6. The compound of claim 5, wherein:

R₁ is substituted or unsubstituted alkyl;

R₂ is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or —

C(O)R_a, where R_a is substituted or unsubstituted alkyl;

R_1a and R_2a together form a covalent bond;

R₃ and R₄ are each independently substituted or unsubstituted alkyl;

R_3a and R_4a are each independently hydrogen, or together form a covalent bond;

R₅ is substituted or unsubstituted alkyl;

R₆ and R_6a together form ═

O;

R₇ is azaalkyl, or azaaralkyl;

R₈ and R_8a together form ═

O;

R₉ and R₁₀ are each independently substituted or unsubstituted alkyl;

each of R₁-R₁₀, when substituted, is substituted with one or more substituents each independently selected from Q, where Q is halo, pseudohalo, haloalkyl, COOR_b where R_b is hydrogen or alkyl, OR_c where R_c is alkyl or aralkyl, NR_fR_g where R_f and R_g are each independently hydrogen, alkyl or aralkyl, or ═

NR_h where R_h is aralkyl;

each Q is independently unsubstituted or is substituted with one or more substituents each independently selected from Q₁, where Q₁ is halo, pseudohalo, or haloalkyl.

7. The compound of claim 5, wherein:

R₁ is unsubstituted alkyl;

R₂ is substituted or unsubstituted alkyl, unsubstituted alkenyl, or —

C(O)R_a, where R_a is unsubstituted alkyl;

R_1a and R_2a together form a covalent bond;

R₃ and R₄ are each independently unsubstituted alkyl;

R_3a and R_4a are each independently hydrogen, or together form a covalent bond;

R₅ is unsubstituted alkyl;

R₆ and R_6a together form ═

O;

R₇ is azaalkyl, or azaaralkyl;

R₈ and R_8a together form ═

O;

R₉ is substituted alkyl;

R₁₀ is unsubstituted alkyl;

each of R₁-R₁₀, when substituted, is substituted with one or more substituents each independently selected from Q, where Q is halo, pseudohalo, haloalkyl, COOR_b where R_b is hydrogen or alkyl, OR_c, where R_c is alkyl or aralkyl, NR_fR_g where R_f and R_g are each independently hydrogen, alkyl or aralkyl, or ═

NR_h where R_h is aralkyl;

each Q is independently unsubstituted or is substituted with one or more substituents each independently selected from Q₁, where Q₁, is halo, pseudohalo, or haloalkyl.

8. The compound of claim 5, wherein:

R₁ is methyl;

R_1a and R_2a together form a covalent bond;

R₃ is methyl;

R₄ is ethyl;

R_3a and R_4a are each independently hydrogen, or together form a covalent bond;

R₅ is methyl;

R₉ is CH₂CH₂COOH or CH₂CH₂COOMe;

R₁₀ is methyl.

9. The compound of claim 5, wherein:

R₂ is CH═

CH₂, CH(OR₂₀)CH₃, C(O)Me, C(═

NR₂₁)CH₃ or CH(NHR₂₁)CH₃;

where R₂₀ is methyl, butyl, heptyl, dodecyl or 3,5-bis(trifluoromethyl)-benzyl; and

R₂₁ is 3,5-bis(trifluoromethyl)benzyl.

10. The compound of claim 5, wherein:

R₇ is ═

NR₂₀, where R₂₀ is methyl, butyl, heptyl, dodecyl or 3,5-bis(tri-fluoromethyl)benzyl.

11. The compound of claim 5 having the formula:

12. The compound of claim 5 having the formula:

13. The compound of claim 5 having the formula:

14. The compound of claim 5 having the formula:

15. The compound of claim 5 having the formula:

16. The compound of claim 5 having the formula:

17. The compound of claim 5 having the formula:

18. The compound of claim 5 having the formula

19. The compound of claim 5 having the formula

20. The compound of claim 5 having the formula

21. The compound of claim 5 having the formula

22. The compound of claim 5 having the formula

89. A pharmaceutical composition, comprising a compound of claim 5 or a pharmaceutically acceptable derivative thereof in a pharmaceutically acceptable carrier.

90. An article of manufacture, comprising packaging material and a compound of claim 5 or a pharmaceutically acceptable derivative of a compound of claim 5 contained within the packaging material, wherein the compound or salt thereof is effective in a photodynamic therapy treatment for ameliorating the symptoms of a hyperproliferative disorder;

and the packaging material includes a label that indicates that the compound or salt thereof is used in a photodynamic therapy treatment for ameliorating the symptoms of a hyperproliferative disorder.

91. The compound of claim 5 or a pharmaceutically acceptable derivative thereof when used for the treatment of hyperproliferative tissue.

92. The compound of claim 5 or a pharmaceutically acceptable derivative thereof when used to detect a hyperproliferative tissue.

93. The compound of claim 5 or a pharmaceutically acceptable derivative thereof when used in a photodynamic therapy.

94. The compound of claim 5 or a pharmaceutically acceptable derivative thereof when used to destroy a target composition within a subject.

95. Use of the compound of claim 5 or a pharmaceutically acceptable derivative thereof for formulation of a medicament for the treatment of hyperproliferative disorders.

96. A method for administering a therapy to a target, comprising:

(i) administering to a subject the compound of claim 5 or a pharmaceutically acceptable derivative thereof that preferentially associates with the target, and

(ii) irradiating the subject with light of a wavelength and total fluence sufficient to produce a therapeutic effect.

97. The method of claim 96, wherein the target is selected from the group consisting of:

a vascular endothelial tissue, a neovasculature tissue, a neovasculature tissue present in an eye, an abnormal vascular wall of a tumor, a solid tumor, a tumor of a head, a tumor of a neck, a tumor of an eye, a tumor of a gastrointestinal tract, a tumor of a liver, a tumor of a breast, a tumor of a prostate, a tumors of a lung, a nonsolid tumor, malignant cells of one of a hematopoietic tissue and a lymphoid tissue, lesions in a vascular system, a diseased bone marrow, and diseased cells in which the disease is one of an autoimmune and an inflammatory disease.

98. The method of claim 96, wherein the target composition is selected from the group consisting of bacteria, viruses, fungi, protozoa, and toxins.

99. The method of claim 96, further comprising the step of allowing sufficient time for any of the compound that is not preferentially associated to the target tissue to clear from non-target tissue of the subject prior to the step of irradiating.

100. The method of claim 96 wherein the compound is conjugated to a targeting agent.

101. The method of claim 100 wherein the targeting agent is one of an antibody or an antibody fragment that is specific in binding with the target tissue.

102. The method of claim 100 wherein the targeting agent is a peptide that is specific in binding with the target tissue.

103. The method of claim 100, wherein the targeting agent is a liposomal preparation.

104. A method of photodynamic therapy for treating hyperproliferative tissue in a subject, comprising:

(i) administering to the subject the compound of claim 5 or a pharmaceutically acceptable derivative thereof that preferentially associates with the hyperproliferative tissue, and

(ii) irradiating the subject with light of a wavelength and fluence sufficient to activate the compound, whereby the hyperproliferative tissue is destroyed or impaired.

105. A method for detecting the presence of a hyperproliferative tissue in a subject comprising:

(i) administering to the subject a sufficient quantity of the compound of claim 5 or a pharmaceutically acceptable derivative thereof that preferentially associates with the hyperproliferative tissue; and

(ii) visualizing the compound within the patient.

106. The method of claim 105 wherein the step of visualizing is accomplished by generating an MRI image of at least a part of the patient'"'"'s body.

107. The method of claim 105 wherein the step of visualizing is accomplished by exposing the conjugated compound with light of sufficient energy to cause the compound to fluoresce.

108. A method for detecting a target in a biological sample, comprising:

(i) adding to the biological sample the compound of claim 5 or a pharmaceutically acceptable derivative thereof that binds to the target; and

(ii) detecting the compound.

109. The method of claim 108, wherein the biological sample is selected from the group consisting of blood, urine, saliva, tears, synovial fluid, sweat, interstitial fluid, sperm, cerebrospinal fluid, ascites fluid, and/or tumor tissue biopsy and circulating tumor cells.

110. A method of diagnosing an infecting agent in a patient, comprising:

(i) conjugating to the compound of claim 5 or a pharmaceutically acceptable derivative thereof a targeting agent specific for the infecting agent, whereby a conjugated compound is formed;

(ii) administering to the patient the conjugated compound; and

(iii) visualizing the conjugated compound within the patient.

111. The method of claim 110 wherein the step of visualizing is accomplished by generating a MRI image of at least a part of the patient'"'"'s body.

112. The method of claim 110 wherein the step of visualizing is accomplished by exposing the conjugated compound with light of sufficient energy to cause the compound to fluoresce.

113. A method of generating an image of a target in a subject, comprising:

(i) administering to the subject the compound of claim 5 or a pharmaceutically acceptable derivative thereof; and

(ii) generating an image of at least a part of the subject to which the compound has preferentially associated.

114. The method of claim 113 wherein the image is a nuclear imaging image.

115. A method of labeling a target tissue for diagnostic radiology, comprising:

(i) administering to a subject the compound of claim 5 or a pharmaceutically acceptable derivative thereof; and

(ii) allowing sufficient time for any compound that is not preferentially associated to the target tissue to clear from non-target tissue of the subject, whereby the target tissue can be distinguished from non-target tissue in an MRI image of the subject.

116. A method of providing a medical therapy to an animal, comprising:

(i) administering to the animal the compound of claim 5 or a pharmaceutically acceptable derivative thereof, and (ii) irradiating the animal with light of a wavelength and fluence sufficient to activate the compound, whereby the hyperproliferative tissue is destroyed or impaired.

117. The compound of claim 5 or a pharmaceutically acceptable derivative thereof when used for the labeling of a target tissue for diagnostic radiology.

118. A kit to treat hyperproliferative disorders, comprising the compound of claim 5 or a pharmaceutically acceptable derivative thereof and instructions teaching a method of photodynamic therapy.

119. A kit to label specific tissues for diagnostic radiology, comprising the compound of claim 5 or a pharmaceutically acceptable derivative thereof and instructions teaching a method of magnetic resonance imaging.

120. A combination, comprising:

the compound of claim 5 or a pharmaceutically acceptable derivative thereof; and

a light source.

121. A combination, comprising:

the compound of claim 5 or pharmaceutically acceptable derivatives thereof; and

a magnetic resonance imaging device.

122. The compound of claim 17 or a pharmaceutically acceptable derivative thereof when used for the detection or treatment or both of hyperproliferative tissue.

123. The compound of claim 18 or a pharmaceutically acceptable derivative thereof when used for the detection or treatment or both of hyperproliferative tissue.

124. The compound of claim 19 or a pharmaceutically acceptable derivative thereof when used for the detection or treatment or both of hyperproliferative tissue.