Radiopharmaceuticals For Diagnosis And Therapy

• US 20070265230A1
• Filed: 05/11/2007
• Published: 11/15/2007
• Est. Priority Date: 05/11/2006
• Status: Active Grant

• Current Assignee: Spectrum Dynamics Medical Ltd
• Original Assignee: Biosensors International Group, Ltd.
• Inventors: Rousso, Benny, Sayada, Chalom
• Granted Patent: US 8,894,974 B2
• Time in Patent Office: Days
• US Class Current: 514/137
• CPC Class Codes: A61K 31/66 Phosphorus compounds
• CPC Class Codes: A61K 49/0004 Screening or testing of compounds for diagnosis of disorders, assessment of conditions, e.g. renal clearance, gastric emptying, testing for diabetes, allergy, rheuma, pancreas functions
• CPC Class Codes: A61K 51/00 Preparations containing radioactive substances for use in therapy or testing in vivo

Abstract

A method for treating a human patient is provided, including administering a radiolabeled form of a therapeutic agent to the patient at a first substantially non-therapeutically-effective dose, wherein pharmacological activity of the therapeutic agent is not due to radioactivity of the therapeutic agent. The method also includes determining information related to a biodistribution of the radiolabeled form of the therapeutic agent in the patient by performing a radioimaging procedure on the patient. Responsively to the information, a decision is made whether or not to treat the patient by administering the therapeutic agent to the patient. If the decision is made to treat the patient, the patient is treated by administering the therapeutic agent to the patient at a second therapeutically-effective dose. If the decision is made not to treat the patient, treatment of the patient with the therapeutic agent is withheld. Other embodiments are also described.

Claims

1. A method for treating a human patient, comprising:

administering a radiolabeled form of a therapeutic agent to the patient at a first substantially non-therapeutically-effective dose, wherein pharmacological activity of the therapeutic agent is not due to radioactivity of the therapeutic agent;

determining information related to a biodistribution of the radiolabeled form of the therapeutic agent in the patient by performing a radioimaging procedure on the patient;

responsively to the information, making a decision whether or not to treat the patient by administering the therapeutic agent to the patient;

if the decision is made to treat the patient, treating the patient by administering the therapeutic agent to the patient at a second therapeutically-effective dose; and

if the decision is made not to treat the patient, withholding treating the patient with the therapeutic agent.

2. The method according to claim 1, wherein making the decision comprises making the decision responsively to a likelihood of an occurrence of an adverse advent caused by the therapeutic agent, determined responsively to the information.

3. The method according to claim 1, wherein making the decision comprises making the decision responsively to a likelihood of treatment success by administering the therapeutic agent, determined responsively to the information.

4. The method according to claim 1, wherein making the decision comprises making the decision responsively to a determination, made responsively to the information, of whether the patient is likely to be a responder to treatment with the therapeutic agent.

5. The method according to claim 1, wherein treating the patient comprises treating the patient by administering a non-radiolabeled form of the therapeutic agent to the patient at the second dose, which non-radiolabeled form of the therapeutic agent is substantially non-radioactive.

6. The method according to claim 1, wherein treating the patient comprises treating the patient by administering the radiolabeled form of the therapeutic agent to the patient at the second dose.

7. The method according to claim 1, wherein treating the patient comprises setting the second therapeutically-effective dose of the therapeutic agent responsively to the information.

8. The method according to claim 7, wherein setting the second dose comprises setting the second dose at a level that reduces a likelihood of an occurrence of an adverse advent caused by the administering the therapeutic agent, determined responsively to the information.

9. The method according to claim 1, wherein the first dose has a total radioactivity per body mass of the patient that is less than 0.05 mCi/kg.

10. The method according to claim 1, wherein the first dose is less than the second dose.

11. The method according to claim 10, wherein the first dose is less than 10% of the second dose.

13. The method according to claim 11, wherein the first dose is less than 1% of the second dose.

15. The method according to claim 13, wherein the first dose is less than 0.1% of the second dose.

16. The method according to claim 1, wherein the radiolabeled form of the therapeutic agent binds to a biological target in a body of the patient having a Molar concentration of less than 10ˆ

-10.

18. The method according to claim 1, wherein administering the radiolabeled form of the therapeutic agent comprises administering the radiolabeled form formed by replacing a non-radioactive isotope of an element of a non-radiolabeled form of the therapeutic agent with a radioactive isotope.

20. The method according to claim 1, wherein administering the radiolabeled form of the therapeutic agent comprises administering the radiolabeled form formed by bonding a radioactive radiotracer to the non-radiolabeled form of the therapeutic agent.

21. The method according to claim 1, wherein the therapeutic agent is selected from the group consisting of:

a protein, an analgesic, an antibiotic, a cardiac drug, a neurological drug, an anti-inflammatory agent, and a non-steroidal anti-inflammatory agent.

23. The method according to claim 1, wherein performing the radioimaging procedure comprises performing a SPECT imaging procedure on the patient.

25. The method according to claim 1, wherein determining the information comprises determining the information related to a time profile of at least a portion of the biodistribution of the radiolabeled form of the therapeutic agent.

26. The method according to claim 1, wherein determining the information comprises determining the information related to an uptake of the radiolabeled form of the therapeutic agent.

27. The method according to claim 1, wherein determining the information comprises determining the information related to metabolism of at least one element selected from the group consisting of:

the radiolabeled form of the therapeutic agent, a substrate of the radiolabeled form of the therapeutic agent, and an enzyme involved in metabolism of the radiolabeled form of the therapeutic agent.

28. The method according to claim 1,

wherein administering the radiolabeled form of the therapeutic agent comprises administering respective radiolabeled forms of a plurality of therapeutic agents to the patient at respective first substantially non-therapeutically-effective doses, wherein the pharmacological activity of the therapeutic agents is not due to radioactivity of the therapeutic agents,

wherein determining the information comprises determining the information related to respective biodistributions of the radiolabeled forms of the therapeutic agents in the patient by performing the radioimaging procedure on the patient,

wherein making the decision comprises making the decision, responsively to the information, whether or not to treat the patient by administering one or more of the plurality of therapeutic agents to the patient, and

wherein, if the decision is made to treat the patient, treating the patient by administering the one or more of the plurality of therapeutic agents to the patient at respective second therapeutically-effective doses.

29. The method according to claim 28, wherein, if the decision is made to treat the patient, treating the patient by administering the one or more of the plurality of therapeutic agents comprises withholding administering at least one other of the plurality of therapeutic agents.

30. The method according to claim 28, wherein making the decision comprises making the decision to treat the patient by administering the one or more of the plurality of therapeutic agents responsively to a determination that the one or more of the plurality of therapeutic agents are more likely to be effective in treating the patient than at least one other of the plurality of therapeutic agents.

31. The method according to claim 28, wherein two or more of the radiolabeled forms of plurality of therapeutic agents are radiolabeled with a same radiotracer.

32. The method according to claim 28, wherein two or more of the radiolabeled forms of plurality of therapeutic agents are radiolabeled with different radiotracers.

33. The method according to claim 28, wherein the plurality of therapeutic agents comprise at least five therapeutic agents.

12. (canceled)

14. (canceled)

17. (canceled)

19. (canceled)

22. (canceled)

24. (canceled)

34. (canceled)

35. A method for treating a human patient, comprising:

administering a radiolabeled form of a therapeutic agent to the patient at a first dose, wherein pharmacological activity of the therapeutic agent is not due to radioactivity of the therapeutic agent;

determining information related to a biodistribution of the radiolabeled form of the therapeutic agent in the patient by performing a radioimaging procedure on the patient;

responsively to the information, setting a second therapeutically-effective dose of the therapeutic agent; and

treating the patient by administering the therapeutic agent to the patient at the second dose.

36. The method according to claim 35, wherein the first dose is substantially not therapeutically effective, and wherein administering the radiolabeled form of the therapeutic agent comprises administering the radiolabeled form of the therapeutic agent at the substantially non-therapeutically-effective first dose.

37. The method according to claim 35, wherein treating the patient by administering the therapeutic agent comprises treating the patient by administering a non-radiolabeled form of the therapeutic agent to the patient at the second dose, which non-radiolabeled form of the therapeutic agent is substantially non-radioactive.

38. The method according to claim 35, wherein treating the patient by administering the therapeutic agent comprises treating the patient by administering the radiolabeled form of the therapeutic agent to the patient at the second dose.

39. The method according to claim 35, wherein setting the second dose comprises setting the second dose at a level that reduces a likelihood of an adverse advent caused by the administering the therapeutic agent, determined responsively to the information.

40. The method according to claim 35, wherein the first dose has a total radioactivity per body mass of the patient that is less than 0.05 mCi/kg.

41. The method according to claim 35, wherein the first dose is less than the second dose.

42. The method according to claim 41, wherein the first dose is less than 10% of the second dose.

44. The method according to claim 42, wherein the first dose is less than 1% of the second dose.

46. The method according to claim 44, wherein the first dose is less than 0.1% of the second dose.

47. The method according to claim 35, wherein the radiolabeled form of the therapeutic agent binds to a biological target in a body of the patient having a Molar concentration of less than 10⁻

10.

49. The method according to claim 35, wherein administering the radiolabeled form of the therapeutic agent comprises administering the radiolabeled form formed by replacing a non-radioactive isotope of an element of a non-radiolabeled form of the therapeutic agent with a radioactive isotope.

51. The method according to claim 35, wherein administering the radiolabeled form of the therapeutic agent comprises administering the radiolabeled form formed by bonding a radioactive radiotracer to the non-radiolabeled form of the therapeutic agent.

52. The method according to claim 35, wherein the therapeutic agent is selected from the group consisting of:

a protein, an analgesic, an antibiotic, a cardiac drug, a neurological drug, an anti-inflammatory agent, and a non-steroidal anti-inflammatory agent.

54. The method according to claim 35, wherein performing the radioimaging procedure comprises performing a SPECT imaging procedure on the patient.

56. The method according to claim 35, wherein determining the information comprises determining the information related to a time profile of at least a portion of the biodistribution of the radiolabeled form of the therapeutic agent.

57. The method according to claim 35, wherein determining the information comprises determining the information related to an uptake of the radiolabeled form of the therapeutic agent.

58. The method according to claim 35, wherein determining the information comprises determining the information related to metabolism of at least one element selected from the group consisting of:

the radiolabeled form of the therapeutic agent, a substrate of the radiolabeled form of the therapeutic agent, and an enzyme involved in metabolism of the radiolabeled form of the therapeutic agent.

43. (canceled)

45. (canceled)

48. (canceled)

50. (canceled)

53. (canceled)

55. (canceled)

59. A method comprising:

providing a radiolabeled form of a therapeutic agent that binds to a biological target in a body of a human patient having a Molar concentration of less than 10<sup>−

10</sup>;

administering the radiolabeled form of the therapeutic agent to the patient at a non-therapeutic dose; and

performing a radioimaging procedure on the patient in conjunction with the administering.

60. The method according to claim 59, wherein pharmacological activity of the therapeutic agent is not due to radioactivity of the therapeutic agent.

61. The method according to claim 59, wherein the biological target has a Molar concentration of less than 10⁻

11.

62. The method according to claim 61, wherein the biological target has a Molar concentration of less than 10⁻

12.

63. The method according to claim 59, wherein administering the radiolabeled form of the therapeutic agent comprises administering the radiolabeled form of the therapeutic agent having a total radioactivity per body mass of the patient that is less than 0.05 mCi/kg.

65. The method according to claim 59, wherein providing the radiolabeled form of the therapeutic agent comprises replacing a non-radioactive isotope of an element of a non-radiolabeled form of the therapeutic agent with a radioactive isotope.

67. The method according to claim 59, wherein providing the radiolabeled form of the therapeutic agent comprises bonding a radioactive radiotracer to a non-radiolabeled form of the therapeutic agent.

68. The method according to claim 59, wherein the therapeutic agent is selected from the group consisting of:

a protein, an analgesic, an antibiotic, a cardiac drug, a neurological drug, an anti-inflammatory agent, and a non-steroidal anti-inflammatory agent.

70. The method according to claim 59, wherein performing the radioimaging procedure comprises performing a SPECT imaging procedure on the patient.

64. (canceled)

66. (canceled)

69. (canceled)

71-123. -123. (canceled)