Radiopharmaceutical Imaging of Neurodegenerative Diseases

• US 20090257949A1
• Filed: 04/03/2009
• Published: 10/15/2009
• Est. Priority Date: 04/04/2008
• Status: Active Grant

• Current Assignee: Avid Radiopharmaceuticals Inc (Eli Lilly and Company)
• Original Assignee: Avid Radiopharmaceuticals Inc (Eli Lilly and Company)
• Inventors: Hefti, Franz F., Carpenter, Alan P. JR., Skovronsky, Daniel M.
• Granted Patent: US 8,557,222 B2
• Time in Patent Office: Days
• US Class Current: 424/1.610
• CPC Class Codes: A61B 6/037 Emission tomography
• CPC Class Codes: A61B 6/508 for non-human patients
• CPC Class Codes: A61K 51/0455 having six-membered rings with one nitrogen as the only ring hetero atom
• CPC Class Codes: A61K 51/0491 Sugars, nucleosides, nucleotides, oligonucleotides, nucleic acids, e.g. DNA, RNA, nucleic acid aptamers

Abstract

Methods for simultaneously detecting dementia or cognitive impairment, such as Alzheimer'"'"'s Disease (AD), Parkinson'"'"'s Disease (PD), Lewy Body Dementia (LBD) and Vascular Dementia (VaD) in a patient using dual or multiple radiopharmaceutical probes are provided herein.

Claims

1. A method for detecting or ruling out multiple neurodegenerative diseased states or pathologic processes in a patient comprising:

administering a first radiopharmaceutical for detecting a structure associated with a first diseased state or pathologic process to a patient;

administering a second radiopharmaceutical for detecting a structure associated with a second diseased state or pathologic process to the patient;

imaging a portion of a brain of the patient comprising a region wherein the structures associated with the first diseased state or pathologic process and the second diseased state or pathologic process are expected to be positioned; and

sequentially detecting the first diseased state or pathologic process and the second diseased state or pathologic process.

2. The method of claim 1, wherein the steps of administering the first radiopharmaceutical and administering the second radiopharmaceutical are performed concurrently.

3. The method of claim 1, wherein the first diseased state is at least one of dementia, cognitive impairment, Alzheimer'"'"'s Disease (AD), Parkinson'"'"'s Disease (PD), Dementia with Lewy Bodies (DLB), Vascular Dementia (VaD), and combinations thereof.

4. The method of claim 1, wherein the second diseased state is at least one of dementia, cognitive impairment, Alzheimer'"'"'s Disease (AD), Parkinson'"'"'s Disease (PD), Dementia with Lewy Bodies (DLB), Vascular Dementia (VaD), and combinations thereof.

5. The method of claim 1, wherein the step of imaging comprises positron emission tomography (PET) imaging, single photon emission computed tomography (SPECT) imaging, PET with concurrent computed tomography imaging (PET/CT), PET with concurrent magnetic resonance imaging (PET/MRI), SPECT with concurrent CT imaging (SPECT/CT), or a combination thereof.

6. The method of claim 1, further comprising the step of waiting for a period of time following administration of the first radiopharmaceutical.

7. The method of claim 1, further comprising the step of waiting for a period of time following administration of the second radiopharmaceutical.

8. The method of claim 1, further comprising the step of administering a third radiopharmaceutical.

9. A method for detecting or ruling out multiple neurodegenerative diseased states or pathologic processes in a patient comprising:

administering a first radiopharmaceutical for detecting a structure associated with a first diseased state or pathologic process to a patient;

administering a second radiopharmaceutical for detecting a structure associated with a second diseased state or pathologic process to the patient;

imaging a portion of a brain of the patient comprising a region wherein the structures associated with the first diseased state or pathologic process and the second diseased state or pathologic process are expected to be positioned; and

concurrently detecting the first diseased state or pathologic process and the second diseased state or pathologic process.

10. The method of claim 9, wherein the steps of administering the first radiopharmaceutical and administering the second radiopharmaceutical are performed concurrently.

11. The method of claim 9, wherein the first diseased state is at least one of dementia, cognitive impairment, Alzheimer'"'"'s Disease (AD), Parkinson'"'"'s Disease (PD), Dementia with Lewy Bodies (DLB), Vascular Dementia (VaD), and combinations thereof.

12. The method of claim 9, wherein the second diseased state is at least one of dementia, cognitive impairment, Alzheimer'"'"'s Disease (AD), Parkinson'"'"'s Disease (PD), Dementia with Lewy Bodies (DLB), Vascular Dementia (VaD), and combinations thereof.

13. The method of claim 9, wherein the step of imaging comprises positron emission tomography (PET) imaging, single photon emission computed tomography (SPECT) imaging, PET with concurrent computed tomography imaging (PET/CT), PET with concurrent magnetic resonance imaging (PET/MRI), SPECT with concurrent CT imaging (SPECT/CT), or a combination thereof.

14. The method of claim 9, further comprising the step of waiting for a period of time following administration of the first radiopharmaceutical.

15. The method of claim 9, further comprising the step of waiting for a period of time following administration of the second radiopharmaceutical.

16. The method of claim 9, further comprising the step of administering a third radiopharmaceutical.

17. A method for detecting or ruling out multiple neurodegenerative diseased states or pathologic processes in a patient comprising:

administering an effective amount of a radiopharmaceutical targeted to β

-amyloid plaque to a patient, wherein the β

-amyloid plaque is associated with a first diseased state or pathologic process;

acquiring an image to detect the presence or absence of the β

-amyloid plaque in the cortical regions of the brain of the patient;

administering an effective amount of a metabolic imaging radiopharmaceutical, wherein the metabolic imaging radiopharmaceutical corresponds to glucose utilization in the brain of the patient and wherein a decrease in the metabolic imaging radiopharmaceutical signal is associated with a second diseased state or pathologic process;

acquiring an image to detect metabolic activity of the brain of the patient;

detecting the presence or absence of the first diseased state or pathologic process; and

detecting the presence or absence of the second diseased state or pathologic process.

18. The method of claim 17, wherein the metabolic imaging radiopharmaceutical comprises ¹⁸FDG.

19. The method of claim 17, wherein the radiopharmaceutical targeted to β

-amyloid plaque comprises ¹⁸F-AV-45.

20. The method of claim 19, wherein the effective amount of ¹⁸F-AV-45 comprises from about 0.1 to about 20 mCi.

21. The method of claim 19, wherein the effective amount of ¹⁸F-AV-45 comprises about 10 mCi.

22. The method of claim 17, wherein the first diseased state is at least one of dementia, cognitive impairment, Alzheimer'"'"'s Disease (AD), Parkinson'"'"'s Disease (PD), Dementia with Lewy Bodies (DLB), Vascular Dementia (VaD), and combinations thereof.

23. The method of claim 17, wherein the second diseased state is at least one of dementia, cognitive impairment, Alzheimer'"'"'s Disease (AD), Parkinson'"'"'s Disease (PD), Dementia with Lewy Bodies (DLB), Vascular Dementia (VaD), and combinations thereof.

24. The method of claim 17, wherein the step of administering the radiopharmaceutical targeted to β

-amyloid plaque and the step of administering the metabolic imaging radiopharmaceutical are performed concurrently.

25. The method of claim 17, wherein the step of acquiring an image to detect the presence or absence of the β

-amyloid plaque in the cortical regions of the brain of the patient and the step of acquiring an image to detect metabolic activity of the brain of the patient are performed concurrently.

26. The method of claim 17, wherein the step of acquiring an image to detect the presence or absence of the β

-amyloid plaque in the cortical regions of the brain of the patient and the step of acquiring an image to detect metabolic activity of the brain of the patient are performed sequentially.

27. The method of claim 17, wherein the steps of acquiring images comprise positron emission tomography (PET) imaging, single photon emission computed tomography (SPECT) imaging, PET with concurrent computed tomography imaging (PET/CT), PET with concurrent magnetic resonance imaging (PET/MRI), SPECT with concurrent CT imaging (SPECT/CT), or a combination thereof.

28. The method of claim 17, further comprising the step of normalizing the image intensity of the acquired images to the cerebellum of the brain of the patient.

29. The method of claim 17, wherein the steps of detecting the first diseased state or pathologic process and detecting the second diseased state or pathologic process are performed sequentially.

30. The method of claim 17, wherein the steps of detecting the first diseased state or pathologic process and detecting the second diseased state or pathologic process are performed concurrently.

31. A method for detecting or ruling out multiple neurodegenerative diseased states or pathologic processes in a patient comprising:

administering an effective amount of a radiopharmaceutical targeted to β

-amyloid plaque to a patient, wherein the β

-amyloid plaque is associated with a first diseased state or pathologic process;

acquiring an image to detect the presence or absence of the β

-amyloid plaque in the cortical regions of the brain of the patient;

administering an effective amount of a radiopharmaceutical targeted to nigrostriatal neurons of the patient, wherein the dopaminergic degeneration of nigrostriatal neurons is associated with a second diseased state or pathologic process;

acquiring an image to detect the dopaminergic degeneration of nigrostriatal neurons in the striatal regions of the brain of the patient;

detecting the presence or absence of the first diseased state or pathologic process; and

detecting the presence or absence of the second diseased state or pathologic process.

32. The method of claim 31, wherein the radiopharmaceutical targeted to β

-amyloid plaque comprises ¹⁸F-AV-45.

33. The method of claim 32, wherein the effective amount of ¹⁸F-AV-45 comprises from about 0.1 to about 20 mCi.

34. The method of claim 32, wherein the effective amount of ¹⁸F-AV-45 comprises about 10 mCi.

35. The method of claim 31, wherein the radiopharmaceutical targeted to nigrostriatal neurons comprises ¹⁸F-AV-133.

36. The method of claim 35, wherein the effective amount of ¹⁸F-AV-133 comprises from about 0.1 to about 20 mCi.

37. The method of claim 35, wherein the effective amount of ¹⁸F-AV-133 comprises about 10 mCi.

38. The method of claim 31, wherein the first diseased state is at least one of dementia, cognitive impairment, Alzheimer'"'"'s Disease (AD), Parkinson'"'"'s Disease (PD), Dementia with Lewy Bodies (DLB), Vascular Dementia (VaD), and combinations thereof.

39. The method of claim 31, wherein the second diseased state is at least one of dementia, cognitive impairment, Alzheimer'"'"'s Disease (AD), Parkinson'"'"'s Disease (PD), Dementia with Lewy Bodies (DLB), Vascular Dementia (VaD), and combinations thereof.

40. The method of claim 31, wherein the step of administering the radiopharmaceutical targeted to β

-amyloid plaque and the step of administering the radiopharmaceutical targeted to nigrostriatal neurons are performed concurrently.

41. The method of claim 31, wherein the step of acquiring an image to detect the presence or absence of the β

-amyloid plaque in the cortical regions of the brain of the patient and the step of acquiring an image to detect the dopaminergic degeneration of nigrostriatal neurons in the striatal regions of the brain of the patient are performed concurrently.

42. The method of claim 31, wherein the step of acquiring an image to detect the presence or absence of the β

-amyloid plaque in the cortical regions of the brain of the patient and the step of acquiring an image to detect metabolic activity of the brain of the patient are performed sequentially.

43. The method of claim 31, wherein the steps of acquiring images comprise positron emission tomography (PET) imaging, single photon emission computed tomography (SPECT) imaging, PET with concurrent computed tomography imaging (PET/CT), PET with concurrent magnetic resonance imaging (PET/MRI), SPECT with concurrent CT imaging (SPECT/CT), or a combination thereof.

44. The method of claim 31, further comprising the step of normalizing the image intensity of the acquired images to the cerebellum of the brain of the patient.

45. The method of claim 31, wherein the steps of detecting the first diseased state or pathologic process and detecting the second diseased state or pathologic process are performed sequentially.

46. The method of claim 31, wherein the steps of detecting the first diseased state or pathologic process and detecting the second diseased state or pathologic process are performed concurrently.

47. A method for detecting or ruling Out Alzheimer'"'"'s Disease (AD) and Vascular Dementia (VaD) in a patient comprising:

administering an effective amount of a radiopharmaceutical targeted to β

-amyloid plaque to a patient, wherein the β

-amyloid plaque is associated with Alzheimer'"'"'s Disease (AD);

acquiring an image to detect the presence or absence of the β

-amyloid plaque in the cortical regions of the brain of the patient;

administering an effective amount of a perfusion imaging radiopharmaceutical, wherein the perfusion imaging radiopharmaceutical indicates blood flow in the brain of the patient and wherein a decrease in the perfusion imaging radiopharmaceutical signal is associated with Vascular Dementia (VaD);

acquiring an image to detect perfusion of the brain of the patient;

detecting the presence or absence of Alzheimer'"'"'s Disease (AD) in the patient; and

detecting the presence or absence of Vascular Dementia (VaD) in the patient.

48. The method of claim 47, wherein the perfusion imaging radiopharmaceutical comprises H₂¹⁵O.

49. The method of claim 47, wherein the perfusion imaging radiopharmaceutical comprises ¹³NH₃.

50. The method of claim 47, wherein the radiopharmaceutical targeted to β

-amyloid plaque comprises ¹⁸F-AV-45.

51. The method of claim 50, wherein the effective amount of ¹⁸F-AV-45 comprises from about 0.1 to about 20 mCi.

52. The method of claim 50, wherein the effective amount of ¹⁸F-AV-45 comprises about 10 mCi.

53. The method of claim 47, wherein the step of administering the radiopharmaceutical targeted to β

-amyloid plaque and the step of administering the perfusion imaging radiopharmaceutical are performed concurrently.

54. The method of claim 47, wherein the step of acquiring an image to detect the presence or absence of the β

-amyloid plaque in the cortical regions of the brain of the patient and the step of acquiring an image to detect perfusion of the brain of the patient are performed concurrently.

55. The method of claim 47, wherein the step of acquiring an image to detect the presence or absence of the β

-amyloid plaque in the cortical regions of the brain of the patient and the step of acquiring an image to detect metabolic activity of the brain of the patient are performed sequentially.

56. The method of claim 47, wherein the steps of acquiring images comprise positron emission tomography (PET) imaging, single photon emission computed tomography (SPECT) imaging, PET with concurrent computed tomography imaging (PET/CT), PET with concurrent magnetic resonance imaging (PET/MRI), SPECT with concurrent CT imaging (SPECT/CT), or a combination thereof.

57. The method of claim 47, further comprising the step of normalizing the image intensity of the acquired images to the cerebellum of the brain of the patient.

58. The method of claim 47, wherein the steps of detecting Alzheimer'"'"'s Disease (AD) and detecting Vascular Dementia (VaD) are performed sequentially.

59. The method of claim 47, wherein the steps of detecting Alzheimer'"'"'s Disease (AD) and detecting Vascular Dementia (VaD) are performed concurrently.