Claims
- 1. A method of treating tumors or cancer in a human in need of such treatment, which comprises:
(a) administering to the human a transfer compound which comprises a chemotherapeutic compound linked to a carrier compound by a bond or a bridging molecule, said carrier compound, bridging molecule or chemotherapeutic compound comprising a pre-selected element; and then (b) irradiating a selected region, in which tumorous or cancerous cells are located, with line emission x-rays of an energy selected to cause emission of Auger electrons from said pre-selected element in a dose effective to disrupt the linkage to said chemotherapeutic compound and thereby release said chemotherapeutic compound in proximity to said cancerous cells.
- 2. A method according to claim 1, wherein the transfer compound is substantially non-toxic.
- 3. A method according to claim 1, wherein the transfer compound has an affinity for both normal and cancerous cells.
- 4. A method according to claim 3, wherein the transfer compound is substantially non-toxic.
- 5. A method according to claim 1, wherein the transfer compound has a selective affinity for cancerous cells.
- 6. A method according to claim 1, wherein the carrier compound is substantially non-toxic.
- 7. A method according to claim 1, wherein the carrier compound has a selective affinity for cancerous cells.
- 8. A method according to claim 7, wherein the carrier compound comprises a tumor receptor ligand.
- 9. A method according to claim 1, wherein the carrier compound is a complex of a ligand and said pre-selected element.
- 10. A method according to claim 9, wherein the ligand is selected from the group consisting of 10-(2-hydroxy-propyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid, diethylenetriamine pentaacetic acid or diethylenetriamine pentaacetic acid bismethylamide.
- 11. A method according to claim 1, wherein the carrier compound is a chelate.
- 12. A method according to claim 11, wherein the chemotherapeutic compound is covalently linked to a reactive carboxyl group of the chelate.
- 13. A method according to claim 1, wherein the chemotherapeutic compound is a taxane.
- 14. A method according to claim 13, wherein the taxane is paclitaxel.
- 15. A method according to claim 13, wherein the taxane is a paclitaxel analog.
- 16. A method according to claim 13, wherein the carrier compound is a gadolinium containing chelate.
- 17. A method according to claim 13, wherein the carrier compound is a tumor receptor ligand comprising said pre-selected element.
- 18. A method according to claim 1, wherein step (b) is performed on cells removed from the human.
- 19. A method according to claim 18, wherein after step (b) is performed, the removed cells are returned to the human.
- 20. A method according to claim 18, wherein after step (b) is performed, the removed cells are transplanted.
- 21. A method according to claim 1, wherein step (a) and step (b) are performed on cells removed from the human.
- 22. A method according to claim 21, wherein after step (b) is performed, the removed cells are returned to the human.
- 23. A method according to claim 21, wherein after step (b) is performed, the removed cells are transplanted.
- 24. A method according to claim 1, wherein the pre-selected element has an atomic number in the range of from 35 to 79.
- 25. A method according to claim 24, wherein the pre-selected element is selected from the group consisting of Ru, I, Gd and Pt.
- 26. A method according to claim 24, wherein the cancerous cells of the human's body are superficial and the pre-selected element is Br.
- 27. A method according to claim 1, wherein the transfer compound is selected to have a high rate of excretion by normal physiological processes.
- 28. A method according to claim 1, wherein the transfer compound is selected for stability against dissociation of the pre-selected element during the time prior to substantially complete excretion or metabolism of the transfer compound.
- 29. A method according to claim 1, wherein the carrier compound is selected to have a high rate of excretion by normal physiological processes.
- 30. A method according to claim 1, wherein the carrier compound comprises said pre-selected element and the carrier compound is selected for stability against dissociation of the pre-selected element during the time prior to substantially complete excretion or metabolism of the carrier compound.
- 31. A method according to claim 1, wherein an end window transmission x-ray tube producing bright line emission x-rays is used for irradiating.
- 32. A method according to claim 31, wherein an e-beam generated in the x-ray tube is focused on a thin target having a thickness of up to about 40 μm, said target being inside the tube and functions as part of the end window.
- 33. A method according to claim 32, wherein the target and the e-beam energy are selected to provide substantially monochromatic line emission x-rays having an energy above and near the K-absorption edge of the pre-selected element.
- 34. A method according to claim 33, wherein the thin target is selected from the group consisting of Mo, Ag, La, Sr and Tm.
- 35. A method according to claim 32, wherein the target and the e-beam energy are selected to provide substantially monochromatic line emission x-rays having an energy above and near the L-absorption edge of the pre-selected element.
- 36. A method according to claim 35, wherein the thin target is Rb.
- 37. A method according to claim 1, wherein Auger electrons are released with a dose of at least about 106 Gy.
- 38. A method according to claim 37, wherein the dose of at least about 106 Gy is released within a distance from the pre-selected element of up to about 10 angstroms.
- 39. A method according to claim 1, wherein step (b) is repeated at least once.
- 40. A method according to claim 39, wherein Auger electrons are released during each repetition of step (b) with a dose of at least about 106 Gy.
- 41. A method according to claim 40, wherein the dose of at least about 106 Gy is released within a distance from the element of the carrier compound of up to about 10 angstroms.
- 42. A method of treating cancer in a human in need of such treatment, which comprises:
(a) administering to the human a transfer compound which comprises a chemotherapeutic compound linked to a carrier compound by a bond or a bridging molecule, said carrier compound, bridging molecule or chemotherapeutic compound comprising a pre-selected element selected from the group consisting of Br, Ru, I, Gd and Pt; and then (b) irradiating at least once, by means of an end window transmission x-ray tube, a selected region, in which cancerous cells are located, with line emission x-rays of an energy selected to cause emission of Auger electrons from said pre-selected element in a dose effective to disrupt the linkage to said chemotherapeutic compound and thereby release said chemotherapeutic compound in proximity to said cancerous cells, said dose for each activation of said x-ray tube being at least about 106 Gy within a distance from the pre-selected element of up to about 10 angstroms.
- 43. A method according to claim 42, wherein the transfer compound is substantially non-toxic.
- 44. A method according to claim 42, wherein the transfer compound has an affinity for both normal and cancerous cells.
- 45. A method according to claim 44, wherein the transfer compound is substantially non-toxic.
- 46. A method according to claim 42, wherein the transfer compound has a selective affinity for cancerous cells.
- 47. A method according to claim 42, wherein the carrier compound is substantially non-toxic.
- 48. A method according to claim 42, wherein the carrier compound has a selective affinity for cancerous cells.
- 49. A method according to claim 48, wherein the carrier compound comprises a tumor receptor ligand.
- 50. A method according to claim 42, wherein the carrier compound is a complex of a ligand and said pre-selected element.
- 51. A method according to claim 50, wherein the ligand is selected from the group consisting of 10-(2-hydroxy-propyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid, diethylenetriamine pentaacetic acid or diethylenetriamine pentaacetic acid bismethylamide.
- 52. A method according to claim 42, wherein the carrier compound is a chelate.
- 53. A method according to claim 52, wherein the chemotherapeutic compound is covalently linked to a reactive carboxyl group of the chelate.
- 54. A method according to claim 42, wherein the chemotherapeutic compound is a taxane.
- 55. A method according to claim 54, wherein the taxane is paclitaxel.
- 56. A method according to claim 54, wherein the taxane is a paclitaxel analog.
- 57. A method according to claim 54, wherein the carrier is a gadolinium containing chelate.
- 58. A method according to claim 54, wherein the carrier compound is a tumor receptor ligand comprising said pre-selected element.
- 59. A method according to claim 42, wherein the transfer compound is selected to have a high rate of excretion by normal physiological processes.
- 60. A method according to claim 42, wherein the transfer compound is selected for stability against dissociation of the pre-selected element time prior to substantially complete excretion or metabolism of the transfer compound.
- 61. A method according to claim 42, wherein the carrier compound is selected to have a high rate of excretion by normal physiological processes.
- 62. A method according to claim 42, wherein the carrier compound comprises said pre-selected element and the carrier compound is selected for stability against dissociation of the pre-selected element during the time prior to substantially complete excretion or metabolism of the carrier compound.
- 63. A method according to claim 42, wherein an e-beam generated in the x-ray tube is focused on a thin target having a thickness of up to about 40 μm, said target being inside the tube and functions as part of the end window.
- 64. A method according to claim 63, wherein the target and the e-beam energy are selected to provide substantially monochromatic line emission x-rays having an energy above and near the K-absorption edge of the pre-selected element.
- 65. A method according to claim 64, wherein the thin target is selected from the group consisting of Sr, Ag, La, and Tm.
- 66. A method according to claim 63, wherein the target and the e-beam energy are selected to provide substantially monochromatic line emission x-rays having an energy above and near the L-absorption edge of the pre-selected element.
- 67. A method according to claim 66, wherein the thin target is Rb.
- 68. A kit for treating tumors or cancer in a human, which comprises:
(1) an x-ray tube having a target comprising a selected metal, said tube being capable of emitting monochromatic line emission x-rays; and (2) a transfer compound which comprises a chemotherapeutic compound linked to a carrier compound by a bond or a bridging molecule, said carrier compound, bridging molecule or chemotherapeutic compound comprising a selected element, the selected metal of said target and the selected element of said transfer compound being selected together:
(a) for said metal of said target to emit line emission x-rays having an energy above and near the K-absorption edge or the L-absorption edge of the selected element of said transfer compound; and (b) for said selected element of said transfer compound to release a dose of Auger electrons upon irradiation by said line emission x-rays.
- 69. A kit according to claim 68, wherein said x-ray tube is an end window transmission x-ray tube capable of emitting bright, line emission x-rays, said x-ray tube comprising an evacuated, elongated chamber having first and second ends, the first end being connected to a power supply, and within said chamber:
electron emitter means near the first end for generating a beam of electrons; an end window transparent to x-rays at the second end, an inner portion of said end window comprising said target; and means for focusing said electron beam on said target.
- 70. A kit according to claim 69, wherein the target has a thickness of up to about 40 μm.
- 71. A kit according to claim 68, wherein the target is selected from the group consisting of Rb, Mo, Ag, La, Sr and Tm.
- 72. A kit according to claim 68, wherein the transfer compound is substantially non-toxic.
- 73. A kit according to claim 68, wherein the transfer compound has an affinity for both normal and cancerous cells.
- 74. A kit according to claim 73, wherein the transfer compound is substantially non-toxic.
- 75. A kit according to claim 68, wherein the transfer compound has a selective affinity for cancerous cells.
- 76. A kit according to claim 68, wherein the carrier compound is substantially non-toxic.
- 77. A kit according to claim 68, wherein the carrier compound has a selective affinity for cancerous cells.
- 78. A kit according to claim 77, wherein the carrier compound comprises a tumor receptor ligand.
- 79. A kit according to claim 68, wherein the carrier compound is a complex of a ligand and said pre-selected element.
- 80. A kit according to claim 79, wherein the ligand is selected from the group consisting of 10-(2-hydroxy-propyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid, diethylenetriamine pentaacetic acid or diethylenetriamine pentaacetic acid bismethylamide.
- 81. A kit according to claim 68, wherein the carrier compound is a chelate.
- 82. A kit according to claim 81, wherein the chemotherapeutic compound is covalently linked to a reactive carboxyl group of the chelate.
- 83. A kit according to claim 68, wherein the chemotherapeutic compound is a taxane.
- 84. A kit according to claim 83, wherein the taxane is paclitaxel.
- 85. A kit according to claim 83, wherein the taxane is a paclitaxel analog.
- 86. A kit according to claim 83, wherein the carrier is a gadolinium containing chelate.
- 87. A kit according to claim 83, wherein the carrier compound is a tumor receptor ligand comprising said selected element.
- 88. A kit according to claim 68, wherein the selected element of the transfer compound has an atomic number in the range of from 35 to 79.
- 89. A kit according to claim 88, wherein the selected element of the transfer compound is selected from the group consisting of Br, Ru, I, Gd and Pt.
- 90. A transfer compound for use in treating cancer or tumors in a human, which comprises:
a chemotherapeutic compound linked to a carrier compound by a bond or a bridging molecule, said carrier compound, bridging molecule or chemotherapeutic compound comprising a pre-selected element; said pre-selected element being capable, when irradiated with line emission x-rays having a selected energy, of emitting Auger electrons in a dose effective to disrupt the linkage to said chemotherapeutic compound.
- 91. A transfer compound according to claim 90, which is substantially non-toxic.
- 92. A transfer compound to claim 90, which has an affinity for both normal and cancerous cells.
- 93. A transfer compound according to claim 92, which is substantially non-toxic.
- 94. A transfer compound according to claim 90, which has a selective affinity for cancerous cells.
- 95. A transfer compound according to claim 90, wherein the carrier compound is substantially non-toxic.
- 96. A transfer compound according to claim 90, wherein the carrier compound has a selective affinity for cancerous cells.
- 97. A transfer compound according to claim 96, wherein the carrier compound comprises a tumor receptor ligand.
- 98. A transfer compound according to claim 90, wherein the carrier compound is a complex of a ligand and said pre-selected element.
- 99. A transfer compound according to claim 98, wherein the ligand is selected from the group consisting of 10-(2-hydroxy-propyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid, diethylenetriamine pentaacetic acid or diethylenetriamine pentaacetic acid bismethylamide.
- 100. A transfer compound according to claim 90, wherein the carrier compound is a chelate.
- 101. A transfer compound according to claim 100, wherein the chemotherapeutic compound is covalently linked to a reactive carboxyl group of the chelate.
- 102. A transfer compound according to claim 90, wherein the chemotherapeutic compound is a taxane.
- 103. A transfer compound according to claim 102, wherein the taxane is paclitaxel.
- 104. A transfer compound according to claim 102, wherein the taxane is a paclitaxel analog.
- 105. A transfer compound according to claim 102, wherein the carrier compound is a gadolinium containing chelate.
- 106. A transfer compound according to claim 102, wherein the carrier compound is a tumor receptor ligand comprising said pre-selected element.
- 107. A transfer compound according to claim 90, wherein the pre-selected element has an atomic number in the range of from 35 to 79.
- 108. A transfer compound according to claim 107, wherein the pre-selected element is selected from the group consisting of Br, Ru, I, Gd and Pt.
- 109. A transfer compound according to claim 90, which when administered has a high rate of excretion by normal physiological processes.
- 110. A transfer compound according to claim 90, which when administered has stability against dissociation of the pre-selected element during the time prior to substantially complete excretion or metabolism of the transfer compound.
- 111. A transfer compound according to claim 90, wherein the carrier compound, when released from the chemotherapeutic compound, has a high rate of excretion by normal physiological processes.
- 112. A transfer compound according to claim 90, wherein the carrier compound comprises said pre-selected element and the carrier compound, when released from the chemotherapeutic compound, has stability against dissociation of the pre-selected element during the time prior to substantially complete excretion or metabolism of the carrier compound.
- 113. A transfer compound according to claim 90, wherein said effective dose is a dose of at least about 106 Gy.
- 114. A transfer compound according to claim 113, wherein said effective dose is a dose of at least about 106 Gy released within a distance from the pre-selected element of up to about 10 angstroms.
- 115. A method of treating tumors or cancer in a human in need of such treatment, which comprises:
(a) administering to the human a compound comprising a pre-selected element; and then (b) irradiating a selected region, in which tumorous or cancerous cells are located, with line emission x-rays of an energy selected to cause emission of Auger electrons from said pre-selected element in a dose effective to disrupt intracellular components of said tumerous or cancerous cells.
- 116. A method according to claim 115, wherein said compound is rose bengal.
- 117. A method according to claim 115, wherein said intracellular components are lysosomes.
- 118. A kit for treating tumors or cancer in a human, which comprises:
(1) an x-ray tube having a target comprising a selected metal, said tube being capable of emitting monochromatic line emission x-rays; and (2) a chemotherapeutic compound comprising a selected element, the selected metal of said target and the selected element of said compound being selected together:
(a) for said metal of said target to emit line emission x-rays having an energy above and near the K-absorption edge or the L-absorption edge of the selected element of said compound; and (b) for said selected element of said compound to release a dose of Auger electrons upon irradiation by said line emission x-rays.
- 119. A kit according to claim 118, wherein said compound is rose bengal.
- 120. A kit according to claim 118, wherein said selected element is iodine.
- 121. A kit according to claim 120, wherein said target is lanthanum.
CROSS-REFERENCES TO RELATED APPLICATIONS
[0001] This application claims the benefit of U.S. Provisional Application No. 60/408,313, filed Sep. 5, 2002.
Provisional Applications (1)
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Number |
Date |
Country |
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60408313 |
Sep 2002 |
US |