In this presentation, Dr. Kwon speaks about a novel method to assess patients who are experiencing a rise in PSA after treatment for prostate cancer. Specifically, he will discuss the utility of C11-choline PET scanning as an emerging technology to determine sites of prostate cancer relapse after initial treatment failure. This will include discussions of identifying sites of local as well as systemic cancer recurrence following initial surgical, radiation, hormonal as well as chemotherapeutic treatment. Dr. Kwon’s presentation will also elucidate how proper identification of sites of prostate cancer recurrence using C11-choline PET plays and instrumental role in determining subsequent steps for optimal therapy including single or multimodality treatment.

1. Let There Be Light
A New Beginning with [11C]-choline PET Imaging
Eugene D Kwon MD Mayo Clinic (Rochester MN)
Professor of Urology and Immunology PCRI 2013

2. Disclosure
Dr. Kwon and Mayo Clinic have received licensing payments
for B7-H (immunotherapeutic) related intellectual
properties from the following entities:
Medarex
Bristol Myers Squibb
Amplimmune
Medimmune
Super PAC: “Equality for All With Kwon as Boss”

4. Scope of the Problem
Prostate cancer that returns after initial therapy represents one of
the most common forms of this disease seen in the clinical setting.
~ 200,000 men in the US will fail prostate cancer treatment
annually.
Of these, ~100,000 men will seek medical evaluation and advice for
“next steps” of treatment for their rising PSA and relapsing cancer.

5. Mayo Clinic – Kwon Clinic
Mayo Clinic (Rochester): ~ 20,000 total and ~4,500 new prostate cancer
patients annually.
Kwon Clinic (Urology): Focuses on management of local / advanced prostate
cancer after failure of prior treatment(s).
• Specialized imaging = [11C]-choline PET imaging (Drs. Lowe, Mullins)
• Minimal Invasive Surgery (Drs. Mynderse, Caldstrom, Atwell)
• Salvage Surgery (Dr. RJ Karnes)
• Stereotactic or Wide-field Radiation (Drs. Olivier, Park, Davis, Choo)
• Chemotherapy (Dr. Quevedo)
• Immunotherapy (Drs. Kwon, Quevedo)

6. Pa
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7. Don’t Treat What You Don’t Understand
ADT
Chemotherapy
Surgery
Zytiga / MDV3100
Cryotherapy
Immunotherapy
Stereotactic or IMRT
Minimal Invasive Surgery
Little (focal) Relapse Big (systemic) Relapse

8. PSA Rising
From Where ?

15. “Riddle Me This”
How can you tell where my
PSA is coming from?

16. [11C]-choline PET Imaging: “Like Doppler Radar”
Shows you where trouble is (within the body)

17. [11C]-choline PET Imaging
‫٭‬ ‫٭‬ = 11C
• Choline is a water-soluble essential nutrient.
• [11C]-choline is a synthetic form of choline that releases a positron (by beta decay)
which can be visualized by Positron Emission Tomography (PET).
• [11C]-choline is rapidly taken up by prostate cancer cells both within and outside
the prostate.

18. Prostate Cancer: [11C]-choline PET Imaging
• Fast, comfortable and safe form of evaluation
• Excellent for assessment when PSA is > 1.0 to 2.0 ng / mL
(Lower PSA Detection Threshold 1.7 -2.0 ng / mL).
• Can evaluate from head to knees.
• Can image whole body (soft tissues, organs, bone) simultaneously.
• Can identify relapsing cancer after all forms of treatment
(surgery, RT, HT, chemotherapy).
• Easy to interpret images
• Mayo has filed for NDA review / approval by FDA (PI, Kwon).
• Is commonly used in Western Europe

19. Prostate Cancer: [11C]-choline PET Imaging
• Superior “single modality” for early detection of relapsing forms of cancer.
(Threshold for detection 1.7-2.0 versus > 20 ng / mL for MRI, CT, bone scan).
• Identifies metabolically active (live) prostate cancer cells as opposed to MRI, CT or
bone scan (which primarily image “static” lesions). The more aggressive the cancer,
the more likely the cancer will be seen with choline PET.
• Can definitely “see” tumors that CT, MRI and bone scan cannot see.
CT MRI
[11C]-choline PET

20. Prostate Cancer: [11C]-choline PET Imaging
• Probably economical relative to current forms of imaging.
• Relatively low levels of irradiation:
• Average background / natural effective dose: 3.6 mSv/year
• Chest x-ray: 0.1-0.2 mSv
• Barium enema: 3-6 mSv
• Coronary angiogram: 5-10 mSv
• NM Bone scan: 3-5 mSv
• Abdomen CT: 7.7 mSv
• Pelvis CT: 7.9 mSv
• Abdomen/Pelvis CT: 14.1 mSv [11C]-choline PET 7.4 - 9.0 mSv
• Chest/Abdomen/Pelvis CT: 20.8 mSv

21. APET i
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• M E T
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• [ 11 d iffer
C]-ch en t fo
oline rm s of
PE T is PE T sc
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up er
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22. [11C]-choline PET Imaging: “Like Doppler Radar”
Shows you where trouble is (within the body)

23. PSA Rising After Definitive Prostate Cancer Treatment
Surgery • Radiation • Cryotherapy • Proton Beam Therapy

24. PSA Rising After Surgery
VU Anastomotic Recurrence: PSA = 0.94 ng/mL
Treated with Cryotherapy
RRP • XRT • ADT

25. PSA Rising After Surgery
SV Recurrence: PSA = 11.3 ng/mL
MRI Choline PET
Treated with XRT + ADT
RRP

26. PSA Rising After Surgery
Pulmonary Hilar Lymph Node Recurrence: PSA = 10.2 ng/mL
Treated with ?
BRT • XRT

27. PSA Rising After Surgery
Pelvic Bone Metastasis: PSA = 2.7 ng/mL
Treated with XRT + ADT
RRP -6m

28. PSA Rising After Surgery
Cervical Spine Metastasis: PSA = 1.7 ng/mL
Treated with XRT + ADT
RRP -4y • XRT (sternal met) -3y

29. PSA Rising After Surgery
Pelvic Lymph Node Metastasis: PSA = 8.1 ng/mL
XRT -10y

30. PSA Rising After Surgery
Extended Pelvic Lymph Node Dissection (Karnes):
PSA = 8.1 → <0.10 ng/mL (x 2y)
No Hormone Therapy
XRT -10y

31. PSA Rising After Cryoprostatectomy
Prostate Recurrence: PSA = 7.6 ng/mL
Treated with XRT
CryoTx -3y

32. PSA Rising After Definitive Prostate Radiation
Prostate Recurrence: PSA = 5.7 ng/mL
Treated with salvage RRP
XRT -9y

33. PSA Rising After Hormone Therapy
Hormone Resistant • Castrate Resistant

36. PSA Rising After Hormone Therapy
L2 Vertebral Metastasis: PSA <0.10 → 1.2 ng/mL
Treated with SBRT
RRP -18y • Orch -17y

37. PSA Rising After Hormone Therapy
Pubic Bone Metastasis: PSA <0.10 → 2.4 ng/mL
Treated with SBRT
RRP -5y • Pelvic RT -2y • ADT -1y

38. PSA Rising After Hormone Therapy
Sternal Metastasis: PSA <0.10 → 5.4 ng/mL
RRP -3y • ADT -3y

39. PSA Rising After Hormone Therapy
Sternal Metastasis: PSA <0.10 → 5.4 ng/mL
Lower Sternal Resection: PSA 5.4 → <0.10 ng/mL (x 2y)
RRP -3y • ADT -3y

40. PSA Rising After Hormone Therapy
C5 Vertebral Metastasis: PSA <0.10 → 1.4 ng/mL
RRP -3y • ADT -3y • Pelvic XRT -6m (no effect)

41. PSA Rising After Hormone Therapy
C5 Vertebral Metastasis: PSA <0.10 → 1.4 ng/mL
C5 Vertebral Resection: PSA 1.4 → <0.10 ng/mL
RRP -3y • ADT -3y • Pelvic XRT -6m (no effect)

42. PSA Rising After Hormone Therapy
Pelvic Lymph Node Metastases x 3: PSA <0.10 → 2.4 ng/mL
MRI [11C]-choline PET
RRP -2y • ADT -2y

43. PSA Rising After Hormone Therapy
Pelvic Lymph Node Metastases x 3: PSA <0.10 → 2.4 ng/mL
Pelvic LN Resection: PSA 2.4 → <0.10 ng/mL (x 1.5y)
RRP -2y • ADT -2y

44. PSA Rising After Hormone Therapy
Periaortic Lymph Node Metastasis: PSA <0.10 → 1.1 ng/mL
XRT -16y • sRRP -11y • ADT 11y

45. PSA Rising After Hormone Therapy
Periaortic Lymph Node Metastasis: PSA <0.10 → 1.1 ng/mL
SBRT Lymph Node: PSA 1.1 → <0.10 ng/mL (x 1y)
XRT -16y • sRRP -11y • ADT 11y

46. PSA Stalled After Systemic Therapy for Metastases
ADT x 1.5y
What To Do?
PSA = > 25,000 ng/mL PSA = 1.1 ng/mL

47. PSA Rising After Systemic Therapy of Metastatic Prostate Cancer
Chemotherapy • Immunotherapy

50. PSA Rising After Systemic Therapy for Metastases
PSA = 68.1 ng/mL
Failed Hormone Therapy • Failed Taxotere Chemotherapy

51. PSA Rising After Systemic Therapy for Metastases
Immunotherapy Given: PSA = 68.1 → 2.7 ng/mL
What To Do?

52. PSA Rising After Systemic Therapy for Metastases
PSA = 147 ng/mL
Failed Hormone Therapy • Failed Taxotere Chemotherapy

53. PSA Rising After Systemic Therapy for Metastases
Immunotherapy Given: PSA = 147 → <0.10 ng/mL
Failed Hormone Therapy • Failed Taxotere Chemotherapy

54. PSA Rising After Systemic Therapy for Metastases
SV recurrence 16 months after Immunotherapy: PSA = <0.10 → 5.0 ng/mL
Failed Hormone Therapy • Failed Taxotere Chemotherapy

55. PSA Rising After Systemic Therapy for Metastases
Treated with Pelvic RT: PSA = 5.0 → <0.10 ng/mL (x 2y)

56. PSA Rising After Systemic Therapy for Metastases
Primary Recurrence: PSA = > 100 → 6.6 → 9.5 ng/mL
MRI Choline PET
Failed XRT • ADT• Immunotherapy • x 5 Chemotherapy

57. PSA Rising After Systemic Therapy for Metastases
Primary Recurrence: PSA = > 100 → 6.6 → 9.5 ng/mL
MRI Choline PET
Treated with salvage RRP (Karnes):
PSA = 9.5 → <0.10 → 0.20 ng/mL (x 1y)
Failed XRT • ADT• Immunotherapy • x 5 Chemotherapy

58. PSA Rising After Systemic Therapy for Metastases
Treated with taxotere chemotherapy x 20 cycles:
PSA = >20 → 0.47 ng/mL
Failed RRP • Failed Immunotherapy • Failed ADT

59. PSA Rising After Systemic Therapy for Metastases
Hip and urethral recurrence: PSA = 0.47 → 2.4 ng/mL
Treated with XRT + Abiraterone (Zytiga):
PSA 2.4 → < 0.10 ng/mL (x 6m)
Failed RRP • Immunotherapy • ADT • Taxotere

60. PSA Rising After Systemic Therapy for Metastases
Sacral Metastasis: PSA = 9.0 ng/mL
Treated with SBRT:
PSA 9.0 → 230 ng/mL (x 1m)
Metastatic Progression

61. PSA Rising After Systemic Therapy for Metastases

63. Conclusions
• [11C]-choline PET imaging is like “night vision” or “Doppler radar”.
• Optimizes therapy by showing what needs to be treated.
“Aim before shooting”
• [11C]-choline PET imaging identifies relapsing CAP at a very early point in
time (small disease volume).
• [11C]-choline PET will probably replace CT / bone scan for CAP.
• Metastases = systemic CAP.
• [11C]-choline PET imaging (or similar) will likely change the way advanced
CAP is treated in the future.

64. Future Directions
• Following response to therapy
• Studying mechanisms of treatment failure
• Observing emergence of CRPC
• Understanding disease homogeneity versus heterogeneity
• New PET scanners and “cocktail” PET scanning
• Better understanding of how to apply multi-modality treatments

65. Thanks
• [11C]-choline PET imaging group: Drs. Lowe, Mullins, Hung
• Minimal Invasive Surgery Group: Drs. Mynderse, Caldstrom, Atwell
• Salvage Surgery Specialist: Dr. Karnes
• Stereotactic or Wide-field RT Group: Drs. Olivier, Park, Davis, Choo.
• Medical Oncology (Chemotherapy) group: Dr. Quevedo
• Immunotherapy Group: Drs. Kwon, Quevedo.
• Nurse Specialists: Diane Mann, Kara Fabel, Rachel See, Melissa Schumacher.
• FDA, PCRI, Dr. Mark Scholz, Dr. Israel Barken.

66. To Schedule Evaluation
Please Contact Administrative Assistant or Nurse (Dr. Kwon):
Ms. Sara Schwantz
Ms. Diane Mann, RN
507-284-1250

67. PSA Rising After Hormone Therapy
Acetabular Metastasis: PSA <0.10 → 1.4 ng/mL
Treated with SBRT
ADT -21m

68. PSA Rising After Systemic Therapy for Metastases
Immunotherapy Given: PSA = 58.5 → 3.5 ng/mL
What To Do?
FDG PET [11C]-choline PET
Failed ADT