Locoregional internal radionuclide ablation of abnormal tissues

1. A method for the locoregional treatment of abnormal tissue, comprising administering a composition comprising an unsealed and non-colloidal radiopharmaceutical to a subject in the region of the abnormal tissue, wherein the radiopharmaceutical is locally sequestered after introduction into the abnormal tissue, and has an effective amount of radioactivity for locoregional ablation of cells in the abnormal tissue, wherein the radiopharmaceutical is selected from the group consisting of Indium-111 chloride ( 111 In—Cl), Yttrium-90 chloride ( 90 YCl 3 ), Copper 61 chloride ( 61 Cu—Cl), Copper 62 chloride ( 62 Cu—Cl), Copper 64 chloride ( 64 Cu—Cl), Gallium 68 chloride ( 68 Ga—Cl), Gallium 67 chloride ( 67 Ga—Cl), Gallium 66 chloride ( 66 Ga—Cl), Gallium 68 citrate ( 68 Ga-citrate), Gallium 67 citrate ( 67 Ga-citrate), Gallium 66 citrate ( 66 Ga-citrate), Iodine-131 sodium iodide (Na 131 I), Holmium-166 DOTMP (166Ho-DOTMP), Samarium-153 EDTMP ( 153 Sm-EDTMP), F-18-2-deoxy-2-fluoro-D-glucose (F-18 FDG), iododeoxyuridine, meta-iodobenzylguanidine, iodocholesterol (NP59), and combinations thereof,

wherein the abnormal tissue comprises a neoplasm, tumor, or synovial tissue,

wherein the administering comprises intratumoral injection, intralesional injection, intramuscular injection, intracavitary injection, interstitial injection, or intrathecal injection, and

wherein the administering comprises administering the composition directly to the abnormal tissue.

2. The method of claim 1 , wherein the subject is human.

3. The method of claim 1 , wherein the radiopharmaceutical is 111 In—Cl, 90 YCl 3 , or F-18 FDG.

4. The method of claim 1 , wherein the radiopharmaceutical is a combination of 111 In—Cl and 90 YCl 3 .

5. The method of claim 1 , wherein the radiopharmaceutical is a combination of F-18 FDG and 111 In—Cl.

6. The method of claim 1 , wherein the radiopharmaceutical is a combination of F-18 FDG and 90YCl 3 .

7. The method of claim 1 , wherein the radiopharmaceutical emits beta radiation, gamma radiation, or positrons.

8. The method of claim 1 , wherein the composition is administered in saline solution.

9. The method of claim 1 further comprising measuring the distribution of the radiopharmaceutical by a method selected from the group consisting of magnetic resonance imaging (MRI), Positron Emission Tomography (PET), Computed Tomography (CT) scanner, Single Photon Emission Computed Tomography (SPECT), ultrasonography, high resolution gamma scintigraphy, and any combination thereof.

10. The method of claim 1 further comprising measuring a radiosensitizer.

11. The method of claim 10 , wherein the radiosensitizer is 2-deoxy-D-glucose.

12. The method of claim 1 further comprising administering Rhodamine-123.

13. The method of claim 1 further comprising administering FeCl 3 or hydrated FeCl 3 .

14. The method of claim 1 further comprising administering a non-radioactive imaging agent.

15. The method of claim 14 , wherein the non-radioactive imaging agent is I-127 NaI, FeCl 3 , hydrated FeCl 3 , Ferrindex, Gadolinium-chloride, or Gadolinium-DTPA.

16. The method of claim 14 , wherein the volume distribution of the radiopharmaceutical is estimated by measuring the distribution of the non-radioactive imaging agent.

17. The method of claim 16 further comprising measuring the distribution of the non-radioactive imaging agent by a method selected from the group consisting of magnetic resonance imaging (MRI), Positron Emission Tomography (PET), Computed Tomography (CT) scanner, Single Photon Emission Computed Tomography (SPECT), ultrasonography, high resolution gamma scintigraphy, and any combination thereof.

18. The method of claim 1 , wherein the radiopharmaceutical is administered to the subject in a large injection volume that covers depths with about a 0.5 cm to 2 cm margin beyond the abnormal tissue.

19. The method of claim 18 , wherein the large injection volume covers depths with about a 1.0 cm to 1.5 cm margin beyond the abnormal tissue.

20. The method of claim 19 , wherein the radiopharmaceutical is 111 In—Cl.

21. The method of claim 1 further comprising administering epinephrine.

22. The method of claim 1 , further comprising administering Calcium-DTPA, Zinc-DTPA, or non-radioactive Iodine to the subject.

23. The method of claim 1 , wherein the Calcium-DTPA, Zinc-DTPA, or non-radioactive Iodine is administered systemically.

24. A method for the locoregional treatment of abnormal tissue, comprising administering a composition comprising an unsealed and non-colloidal radiopharmaceutical to a subject in the region of the abnormal tissue, wherein the radiopharmaceutical comprises an effective amount of radioactivity for locoregional ablation of cells in the abnormal tissue before diffusing away from the site of administration, wherein the radiopharmaceutical is selected from the group consisting of Indium-111 chloride ( 111 In—Cl), Yttrium-90 chloride ( 90 YCl 3 ), Copper 61 chloride ( 61 Cu—Cl), Copper 62 chloride ( 62 Cu—Cl), Copper 64 chloride ( 64 Cu—Cl), Gallium 68 chloride ( 68 Ga—Cl), Gallium 67 chloride ( 67 Ga—Cl), Gallium 66 chloride ( 66 Ga—Cl), Gallium 68 citrate ( 68 Ga-citrate), Gallium 67 citrate ( 67 Ga-citrate), Gallium 66 citrate ( 66 Ga-citrate), Iodine-131 sodium iodide (Na 131 I), Holmium-166 DOTMP ( 166 Ho-DOTMP), Samarium-153 EDTMP ( 153 Sm-EDTMP), F-18-2-deoxy-2-fluoro-D-glucose (F-18 FDG), iododeoxyuridine, meta-iodobenzylguanidine, iodocholesterol (NP59), and combinations thereof,

wherein the abnormal tissue comprises a neoplasm, tumor, or synovial tissue,

wherein the administering comprises intratumoral injection, intralesional injection, intramuscular injection, intracavitary injection, interstitial injection, or intrathecal injection, and

wherein the administering comprises administering the composition directly to the abnormal tissue.

25. A method for the locoregional treatment of tissues surrounding a post-surgical cavity, comprising administering a composition comprising an unsealed and non-colloidal radiopharmaceutical directly to tissues surrounding a post-surgical cavity in a subject, wherein the radiopharmaceutical has an effective amount of radioactivity for locoregional ablation of abnormal cells in the tissues before diffusing away from the site of introduction, wherein the radiopharmaceutical is selected from the group consisting of Indium-111 chloride ( 111 In—Cl), Yttrium-90 chloride ( 90 YCl 3 ), Copper 61 chloride ( 61 Cu—Cl), Copper 62 chloride ( 62 Cu—Cl), Copper 64 chloride ( 64 Cu—Cl), Gallium 68 chloride ( 68 Ga—Cl), Gallium 67 chloride ( 67 Ga—Cl), Gallium 66 chloride ( 66 Ga—Cl), Gallium 68 citrate ( 68 Ga-citrate), Gallium 67 citrate ( 67 Ga-citrate), Gallium 66 citrate ( 66 Ga-citrate), Iodine-131 sodium iodide (Na 131 I), Holmium-166 DOTMP ( 166 Ho-DOTMP), Samarium-153 EDTMP ( 153 Sm-EDTMP), F-18-2-deoxy-2-fluoro-D-glucose (F-18FDG), iododeoxyuridine, meta-iodobenzylguanidine, iodocholesterol (NP59), and combinations thereof, and

wherein the administering comprises intratumoral injection, intralesional injection, intramuscular injection, intracavitary injection, interstitial injection, or intrathecal injection.

26. The method of claim 25 , wherein the tissues surrounding the post-surgical cavity comprises unresectable micrometastases.

27. The method of claim 25 , wherein the radiopharmaceutical is administered to the subject in a large injection volume that covers depths with about a 0.5 cm to 2 cm margin beyond the post-surgical cavity.

28. The method of claim 27 , wherein the large injection volume covers depths with about a 1.0 cm to 1.5 cm margin beyond the post-surgical cavity.

29. The method of claim 28 , wherein the radiopharmaceutical is 111 In—Cl.

30. The method of claim 25 , wherein the composition has a basic pH.

31. The method of claim 30 , wherein the pH is from about 7.0 to about 9.0.

32. The method of claim 30 , wherein the pH is up to about 14.0.

33. The method of claim 25 , wherein the volume of the administered composition is at least about one tenth of one milliliter.

34. The method of claim 1 , wherein the composition has a basic pH.

35. The method of claim 34 , wherein the pH is from about 7.0 to about 9.0.

36. The method of claim 34 , wherein the pH is up to about 14.0.

37. The method of claim 1 , wherein the volume of the administered composition is at least about one tenth of one milliliter.

38. The method of claim 24 , wherein the composition has a basic pH.

39. The method of claim 38 , wherein the pH is from about 7.0 to about 9.0.

40. The method of claim 38 , wherein the pH is up to about 14.0.

41. The method of claim 24 , wherein the volume of the administered composition is at least about one tenth of one milliliter.

42. A method for the locoregional treatment of abnormal tissue, comprising administering a composition comprising an unsealed and non-colloidal radiopharmaceutical to a subject in the region of the abnormal tissue, wherein the radiopharmaceutical is locally sequestered after introduction into the abnormal tissue, and has an effective amount of radioactivity for locoregional ablation of cells in the abnormal tissue, wherein the radiopharmaceutical comprises a free radioactive metal ion selected from the group consisting of In-111, Y-90, Cu-61, Cu-62, Cu-64, Ga-66, Ga-67, Ga-68, Ho-166, Sm-153, and combinations thereof,

wherein the abnormal tissue comprises a neoplasm, tumor, or synovial tissue,

wherein the administering comprises intratumoral injection, intralesional injection, intramuscular injection, intracavitary injection, interstitial injection, or intrathecal injection, and

wherein the administering comprises administering the composition directly to the abnormal tissue.

43. The method of claim 42 , wherein the free radioactive metal ion comprises Y-90.

44. The method of claim 42 , wherein the free radioactive metal ion comprises Ho-166.

45. The method of claim 44 , wherein the radiopharmaceutical further comprises a second free radioactive metal ion.

46. The method of claim 45 , wherein the second free radioactive metal ion is selected from the group consisting of In-111, Y-90, Cu-61, Cu-62, Cu-64, Ga-66, Ga-67, Ga-68, and Sm-153.

47. The method of claim 42 , wherein the free radioactive metal ion comprises Sm-153.

48. The method of claim 42 , wherein the free radioactive metal ion is selected from the group consisting of In-111, Cu-61, Cu-62, Cu-64, Ga-66, Ga-67, Ga-68, and combinations thereof.

49. The method of claim 42 , wherein the composition has a basic pH.

50. The method of claim 49 , wherein the pH is from about 7.0 to about 9.0.

51. The method of claim 49 , wherein the pH is up to about 14.0.

52. The method of claim 42 , wherein the volume of the administered composition is at least about one tenth of one milliliter.

53. A method for the locoregional treatment of abnormal tissue, comprising administering a composition comprising an unsealed and non-colloidal radiopharmaceutical to a subject in the region of the abnormal tissue, wherein the radiopharmaceutical is locally sequestered after introduction into the abnormal tissue, and has an effective amount of radioactivity for locoregional ablation of cells in the abnormal tissue, wherein the radiopharmaceutical is selected from the group consisting of Indium-111 chloride ( 111 In—Cl), Yttrium-90 chloride ( 90 YCl 3 ), Copper 61 chloride ( 61 Cu—Cl), Copper 62 chloride ( 62 Cu—Cl), Copper 64 chloride ( 64 Cu—Cl), Gallium 68 chloride ( 68 Ga—Cl), Gallium 67 chloride ( 67 Ga—Cl), Gallium 66 chloride ( 66 Ga—Cl), Gallium 68 citrate (68Ga-citrate), Gallium 67 citrate ( 67 Ga-citrate), Gallium 66 citrate ( 66 Ga-citrate), Iodine-131 sodium iodide (Na 131 I, Holmium-166 DOTMP ( 166 Ho-DOTMP), Samarium-153 EDTMP ( 153 Sm-EDTMP), F-18-2-deoxy-2-fluoro-D-glucose (F-18 FDG), iododeoxyuridine, meta-iodobenzylguanidine, iodocholesterol (NP59), and combinations thereof, wherein the composition has a basic pH,

wherein the abnormal tissue comprises a neoplasm, tumor, or synovial tissue,

wherein the administering comprises intratumoral injection, intralesional injection, intramuscular injection, intracavitary injection, interstitial injection, or intrathecal injection, and

wherein the administering comprises administering the composition directly to the abnormal tissue.

54. A method for the locoregional treatment of abnormal tissue, comprising administering a composition comprising an unsealed and non-colloidal radiopharmaceutical to a subject in the region of the abnormal tissue, wherein the radiopharmaceutical comprises an effective amount of radioactivity for locoregional ablation of cells in the abnormal tissue before diffusing away from the site of administration, wherein the radiopharmaceutical is selected from the group consisting of Indium-111 chloride ( 111 In—Cl), Yttrium-90 chloride ( 90 YCl 3 ), Copper 61 chloride ( 61 Cu—Cl), Copper 62 chloride ( 62 Cu—Cl), Copper 64 chloride ( 64 Cu—Cl), Gallium 68 chloride ( 68 Ga—Cl), Gallium 67 chloride ( 67 Ga—Cl), Gallium 66 chloride ( 66 Ga—Cl), Gallium 68 citrate ( 68 Ga-citrate), Gallium 67 citrate ( 67 Ga-citrate), Gallium 66 citrate ( 66 Ga-citrate), Iodine-131 sodium iodide (Na 131 I), Holmium-166 DOTMP ( 166 Ho-DOTMP), Samarium-153 EDTMP ( 153 Sm-EDTMP), F-18-2-deoxy-2-fluoro-D-glucose (F-18 FDG), iododeoxyuridine, meta-iodobenzylguanidine, iodocholesterol (NP59), and combinations thereof, wherein the composition has a basic pH,

wherein the abnormal tissue comprises a neoplasm, tumor, or synovial tissue,

wherein the administering comprises intratumoral injection, intralesional injection, intramuscular injection, intracavitary injection, interstitial injection, or intrathecal injection, and

wherein the administering comprises administering the composition directly to the abnormal tissue.

55. A method for the locoregional treatment of tissues surrounding a post-surgical cavity, comprising administering a composition comprising an unsealed and non-colloidal radiopharmaceutical directly to tissues surrounding a post-surgical cavity in a subject, wherein the radiopharmaceutical has an effective amount of radioactivity for locoregional ablation of abnormal cells in the tissues before diffusing away from the site of introduction, wherein the radiopharmaceutical is selected from the group consisting of Indium-111 chloride ( 111 In—Cl), Yttrium-90 chloride ( 90 YCl 3 ), Copper 61 chloride ( 61 Cu—Cl), Copper 62 chloride ( 62 Cu—Cl), Copper 64 chloride ( 64 Cu—Cl), Gallium 68 chloride ( 68 Ga—Cl), Gallium 67 chloride ( 67 Ga—Cl), Gallium 66 chloride ( 66 Ga—Cl), Gallium 68 citrate ( 68 Ga-citrate), Gallium 67 citrate ( 67 Ga-citrate), Gallium 66 citrate ( 66 Ga-citrate), Iodine-131 sodium iodide (Na 131 I), Holmium-166 DOTMP ( 166 Ho-DOTMP), Samarium-153 EDTMP ( 153 Sm-EDTMP), F-18-2-deoxy-2-fluoro-D-glucose (F-18FDG), iododeoxyuridine, meta-iodobenzylguanidine, iodocholesterol (NP59), and combinations thereof, wherein the composition has a basic pH, and

wherein the administering comprises intratumoral injection, intralesional injection, intramuscular injection, intracavitary injection, interstitial injection, or intrathecal injection.