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  1. 1. P ositron E mission T omography in Clinical Oncology <ul><ul><li>Chun Ki Kim, M.D. </li></ul></ul><ul><ul><li>Mount Sinai School of Medicine </li></ul></ul><ul><ul><li>New York, New York </li></ul></ul>
  2. 4. Commonly used PET Radiotracers <ul><li>[F-18] FDG - Glucose metabolism </li></ul><ul><li>[C-11] Methionine - Amino acid transport </li></ul><ul><li>- Incorporation of amino acid </li></ul><ul><li> into protein fractions </li></ul><ul><li>[O-15] Water - Blood flow </li></ul><ul><li>[N-13] Ammonia - Blood flow </li></ul><ul><li>Rb-82 - Blood flow </li></ul>
  3. 5. <ul><li>[C-11] Thymidine Tumor cellular proliferation rate </li></ul><ul><li>[C-11] Aminoisobutyric acid Tumor amino acid uptake </li></ul><ul><li>[F-18] 5-FU Prediction/evaluation of ChemoTx </li></ul><ul><li>[C-11] Tyrosine Tumor metabolism </li></ul><ul><li>[N-13] Glutamate Tumor metabolism </li></ul><ul><li>[C-11] Acetate Myocardial oxidative metabolism </li></ul><ul><li>[C-11] Palmitate Myocardial fatty acid metabolism </li></ul><ul><li>[F-18] FluoroDOPA Dopamine synthesis </li></ul><ul><li>Many other receptor agents Dopamine, serotonin, opiate etc. </li></ul>Potential PET Radiotracers
  4. 6. PET Radiotracer approved by FDA <ul><li>[F-18] FDG (fluoro deoxyglucose) </li></ul><ul><li> Malignancy ~  Glucose / FDG uptake </li></ul>
  5. 8. NORMAL TUMOR <ul><li>Overexpression of Glucose transporters </li></ul><ul><li>Higher levels of Hexokinase </li></ul><ul><li>Down-regulation of Glucose-6-phosphatase </li></ul><ul><li>Anaerobic glycolysis, less ATP per glucose molecule, </li></ul><ul><li>more glucose molecules needed for ATP production </li></ul><ul><li>General increase in metabolism from high growth rates </li></ul>
  6. 9. <ul><li>Malignancy  Glucose/FDG uptake </li></ul>
  7. 10. Gallium PET
  8. 11. Metastatic Thyroid Ca. to Lung, Mediastinum, and Skeleton
  9. 13. General Indications for FDG-PET Tumor Imaging <ul><ul><ul><li>DDx: Benign versus Malignant </li></ul></ul></ul><ul><ul><ul><li>Staging & Restaging </li></ul></ul></ul><ul><ul><ul><li>Metastatic work up: Rising tumor markers </li></ul></ul></ul><ul><ul><ul><li>Monitoring treatment response </li></ul></ul></ul><ul><ul><ul><li>Scar/necrosis/fibrosis vs. Recurrent/residual disease </li></ul></ul></ul><ul><ul><ul><li>Grading/Prognosis </li></ul></ul></ul><ul><ul><ul><li>Detection of unknown primary </li></ul></ul></ul>
  10. 14. New Medicare Coverage Policy for FDG PET <ul><li>Lung Ca (NSC): Dx, Staging & restaging </li></ul><ul><li>Esophgeal Ca: Dx, Staging & restaging </li></ul><ul><li>Colorectal Ca: Dx, Staging & restaging </li></ul><ul><li>Lymphoma: Dx, Staging & restaging </li></ul><ul><li>Melanoma: Dx, Staging & restaging, </li></ul><ul><li>Non-covered for evaluating regional nodes </li></ul><ul><li>Head & Neck Ca: Dx, Staging & restaging </li></ul>
  11. 15. Lung Cancer <ul><ul><ul><li>Dx: Solitary Pulmonary Nodule </li></ul></ul></ul><ul><ul><ul><li>Staging </li></ul></ul></ul><ul><ul><ul><li>Metastatic work-up </li></ul></ul></ul>
  12. 16. Solitary Pulmonary Nodule <ul><li>Incidence detected by CXR: 130,000/year. </li></ul><ul><li>50-60% : Benign </li></ul><ul><li>20-40%: Invasive nodule biopsy </li></ul><ul><li> Resection. </li></ul>
  13. 17. CT: an indeterminant LUL nodule.
  14. 19. Efficacy of PET Solitary Pulmonary Nodule <ul><li>Sensitivity = 97% </li></ul><ul><li>Specificity = 78% </li></ul><ul><li> (Meta-analysis of >40 articles: Gould et al. JAMA 2001 ) </li></ul>
  15. 20. False Positives: Active Infection/Inflammation TB Pneumonia Cryptococcosis Histoplasmosis Aspergillosis Inflammatory
  16. 21. Staging
  17. 24. 60/M: Lung Ca.
  18. 25. 62y/o Lung Ca. with adrenal mass
  19. 27. Colorectal Cancer: Clinical Indications for PET Imaging <ul><ul><ul><li>Staging before primary resection? </li></ul></ul></ul><ul><ul><ul><li>Detection of Lesions after Primary Resection </li></ul></ul></ul><ul><ul><ul><ul><li>Staging before resection of recurrent disease. </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Rising CEA in the absence of a known source. </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Equivocal/residual lesion on conventional imaging. </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Patient is clinically symptomatic, but CEA is normal. </li></ul></ul></ul></ul><ul><ul><ul><li>Monitoring treatment response (pre-op & post-op) </li></ul></ul></ul>
  20. 28. Staging before resection of recurrent disease
  21. 29. 63 y/o woman with a H/O Colon Ca. and liver metastases
  22. 30. 79/M. Resection of Rectal Ca (Dukes B) 4 mos earlier,  CEA, CT: possible local relapse.
  23. 31. T1 T2 T1 enhanced T1 enhanced <ul><li>F/68 </li></ul><ul><li>H/O Colon Ca. </li></ul><ul><li>Rising CEA </li></ul><ul><li>CT/MRI; multiple cysts </li></ul>
  24. 32. Sagittal Transverse Coronal
  25. 33. <ul><li>YW: Colon Ca </li></ul><ul><li>3/00: (-) CT </li></ul><ul><li>5/00: rising CEA </li></ul><ul><li>6/00: (+) PET </li></ul><ul><li>7/00: CT </li></ul>
  26. 34. 58/M - S/P Colon Ca Rising CEA Coronal Coronal Transverse
  27. 35. 58/M - S/P Colon Ca Rising CEA Local recurrence Hemangioma
  28. 36. <ul><li>48y/o with Colon Ca. </li></ul><ul><li>S/P Primary resection. </li></ul><ul><li>S/P Resection of liver </li></ul><ul><li>lesion </li></ul><ul><li>Now with  CEA </li></ul><ul><li>CT: (-) for mets </li></ul>
  29. 37. <ul><li>48y/o with Colon Ca. </li></ul><ul><li>S/P Primary resection. </li></ul><ul><li>S/P Resection of liver </li></ul><ul><li>lesion </li></ul><ul><li>Now with  CEA </li></ul><ul><li>CT: (-) for mets </li></ul>
  30. 38. N. G. 8/15/00 Colon cancer with a Hx of UC Proven mesenteric carcinomatosis
  31. 39. 1756441
  32. 40. Huebner et al. J Nucl Med 2000;41:1177-1189
  33. 41. Huebner et al. J Nucl Med 2000;41:1177-1189
  34. 42. Colorectal Cancer: A possible algorithm CT evidence of resectable disease in patient suitable for surgery Whole Body PET imaging
  35. 43. Colorectal Cancer: A possible algorithm CT evidence of resectable disease in patient suitable for surgery Whole Body PET imaging Further evaluation of CT abnormality All sites negative
  36. 44. Colorectal Cancer: A possible algorithm CT evidence of resectable disease in patient suitable for surgery Whole Body PET imaging Further evaluation of CT abnormality Surgery All sites negative PET = CT and other sites negative
  37. 45. Colorectal Cancer: A possible algorithm CT evidence of resectable disease in patient suitable for surgery Whole Body PET imaging Further evaluation of CT abnormality Non-surgical management Surgery All sites negative + ve at multiple Sites PET = CT and other sites negative
  38. 46. 44/F with Colon Ca, S/P primary resection. CT: multiple liver mets and a lung nodule Treated with systemic chemoTx instead of intra-arterial chemoTx . Staging:
  39. 47. Colorectal Cancer: Clinical Indications for PET Imaging <ul><ul><ul><li>Detection of Lesions </li></ul></ul></ul><ul><ul><ul><ul><li>Staging before resection of recurrent disease. </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Rising CEA in the absence of a known source. </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Equivocal/residual lesion on conventional imaging. </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Patient is clinically symptomatic, but CEA is normal. </li></ul></ul></ul></ul><ul><ul><ul><li>Monitoring treatment response (pre-op & post-op) </li></ul></ul></ul><ul><ul><ul><li>Staging before primary resection? </li></ul></ul></ul>
  40. 48. S/P ChemoRx
  41. 49. Before 2mo after Adjuvant chemo and radioTx Prior to surgery for rectal Ca.
  42. 50. Optimal time to scan after treatment?? Uptake may be seen in inflammatory tissue / macrophages. Residual FDG activity after treatment: Not always active tumor <ul><li>1 month after Chemo. </li></ul><ul><ul><li>PET findings at 1 mo ~ CT findings at 3 mos </li></ul></ul><ul><ul><li>Findlay et al. J Clin Oncol 1996 </li></ul></ul><ul><li>Several months after RT? </li></ul>
  43. 51. Lymphoma: Indications for PET Imaging <ul><ul><ul><li>Dx </li></ul></ul></ul><ul><ul><ul><li>Staging </li></ul></ul></ul><ul><ul><ul><li>Monitoring treatment response </li></ul></ul></ul><ul><ul><ul><li>Recurrence? </li></ul></ul></ul>
  44. 52. Evaluation of early therapeutic response: Is treatment effective? FDG uptake represents cell viability. <ul><ul><ul><li>FDG uptake can be markedly decreased or even completely suppressed after 1 or 2 cycles of chemotherapy </li></ul></ul></ul><ul><ul><ul><li>Early determination is important: To avoid the toxicity of ineffective therapy. To allow selection of a new therapeutic regimen. </li></ul></ul></ul>
  45. 53. 1846641 Lymphoma Before After 2 cylcles of Chemo
  46. 54. Lymphoma Before After 2 cylcles of Chemo
  47. 55. 56y/o : Lymphoma
  48. 56. Before 1 month after XRT
  49. 57. Esophageal/Gastro-esophageal Cancer: Clinical Indications for PET Imaging <ul><ul><ul><li>Pre-op staging </li></ul></ul></ul><ul><ul><ul><li>Monitoring treatment response </li></ul></ul></ul><ul><ul><ul><li>Suspected recurrence </li></ul></ul></ul><ul><ul><ul><li>Prognostication </li></ul></ul></ul>
  50. 58. Esophageal/ Gastro-esophageal Cancer: Clinical Indications for PET Imaging <ul><ul><ul><li>Pre-op staging </li></ul></ul></ul><ul><ul><ul><ul><li>CT: Limited sensitivity </li></ul></ul></ul></ul><ul><ul><ul><ul><li>EUS: More accurate for assessing local invasion and regional nodal mets. </li></ul></ul></ul></ul><ul><ul><ul><li> Limitations: stenosis, </li></ul></ul></ul><ul><ul><ul><li>celiac, </li></ul></ul></ul><ul><ul><ul><li>right hepatic lobe, peritoneum </li></ul></ul></ul>
  51. 59. ( Choi et al: J Nucl Med 2000) Evaluation of N stage of patients with Esophageal Cancer: 48 patients underwent esohagectomy and lymph node dissection (2 field=35pts, 3 field=13pts)
  52. 60. Evaluation of metastases in Esophageal Cancer: CT versus PET CT PET Kole 1998 Lymph nodes 62% 90% Resectability 65% 88% Choi 2000 Lymph nodes 78% 86% N staging 60% 83% Luketich 1999 Distant mets 63% 84%
  53. 61. Rt. Paratracheal Subcarinal Lt. Gastric Common hepatic & Celiac Rt. Paratracheal Subcarinal Lt. Gastric Common hepatic & Celiac
  54. 62. 62F: Gastric Ca. S/P Resection CT: Recurrence PET performed to exclude other sites of tumor Ultrasound: confirmed a liver mets Surgery cancelled and the patient treated with Chemo
  55. 64. Gastro-esophageal Cancer: Clinical Indications for PET Imaging <ul><ul><ul><li>Pre-op staging </li></ul></ul></ul><ul><ul><ul><li>Monitoring treatment response </li></ul></ul></ul><ul><ul><ul><li>Suspected recurrence </li></ul></ul></ul><ul><ul><ul><li>Prognostication </li></ul></ul></ul>
  56. 65. Before sagittal coronal After Radiochemo 49M: large squamous esophageal Ca. Echo-endoscopy – an enlarged node
  57. 66. Gastro-esophageal Cancer: Clinical Indications for PET Imaging <ul><ul><ul><li>Pre-op staging </li></ul></ul></ul><ul><ul><ul><li>Monitoring treatment response </li></ul></ul></ul><ul><ul><ul><li>Suspected recurrence </li></ul></ul></ul><ul><ul><ul><li>Prognostication </li></ul></ul></ul>
  58. 67. 45M: S/P esophagectomy, Patient is clinically asymptomatic  alkaline phosphatase
  59. 68. Gastro-esophageal Cancer: Clinical Indications for PET Imaging <ul><ul><ul><li>Pre-op staging </li></ul></ul></ul><ul><ul><ul><li>Monitoring treatment response </li></ul></ul></ul><ul><ul><ul><li>Suspected recurrence </li></ul></ul></ul><ul><ul><ul><li>Prognostication </li></ul></ul></ul>
  60. 69. Surviavl based on initial PET scan identification of distant versus local disease only: (Luketich et al: Ann Thorac Surg 1999;68)
  61. 70. Pancreatic Cancer: Potential Indications for PET Imaging <ul><ul><ul><li>DDx: Chronic pancreatic mass vs. Cancer </li></ul></ul></ul><ul><ul><ul><li>Staging: Nodal mets and liver mets. </li></ul></ul></ul><ul><ul><ul><li>Monitoring treatment response </li></ul></ul></ul><ul><ul><ul><li>Prognostication </li></ul></ul></ul>
  62. 71. 53/F: Pancreatic mass
  63. 72. 51F: CT: (1) Mass forming pancreatitis vs Cancer (2) Hepatic Hemangioma vs Metastasis Coronal Sagittal
  64. 73. Pancreatic Cancer: DDx: Chronic pancreatic mass vs. Cancer Delbeke et al: J Nucl Med 1999
  65. 74. Brain Tumor <ul><ul><ul><li>Grading </li></ul></ul></ul><ul><ul><ul><li>Prognosis/Survival. </li></ul></ul></ul><ul><ul><ul><li>Necrosis or Residual disease after radiation therapy? </li></ul></ul></ul>
  66. 75. High Grade Low Grade
  67. 76. Kim CK et al. J Neuro-Oncol 1991
  68. 78. Thyroid Cancer Thyroglobulin (+) Iodine-131 scan (-) <ul><ul><ul><li>FDG PET scan is useful. </li></ul></ul></ul>
  69. 79. I V M L FDG-PET I-131 Anterior Posterior M 2 Coronal slices
  70. 80. 62 y/o male S/P Resection of transglottic right laryngeal cancer R/O Recurrence
  71. 81. FDG PET Imaging Determination of the site of unknown primary tumor 20~30%
  72. 82. Prediction of tumor response to treatment: Will the tumor respond to treatment? <ul><ul><ul><li>Labeled Estrogen </li></ul></ul></ul><ul><ul><ul><li>[F-18] 5-Fluorouracil (5-FU) </li></ul></ul></ul>
  73. 83. FDG-PET Tumor Imaging <ul><ul><ul><li>DDx: Is the lesion benign or malignant? </li></ul></ul></ul><ul><ul><ul><li>Staging: Re-staging: </li></ul></ul></ul><ul><ul><ul><li>Evaluation of early therapeutic response: </li></ul></ul></ul><ul><ul><ul><li>Scar/Necrosis vs recurrent/residual disease after surgery. Scar/Necrosis vs recurrent/residual disease after XRT. </li></ul></ul></ul><ul><ul><ul><li>Histologic grading / P rognosis . </li></ul></ul></ul><ul><ul><ul><li>Detection of unknown primary. </li></ul></ul></ul>
  74. 84. Summary: PET <ul><li>Safe. </li></ul><ul><li>Shows all the organ systems of the body with one image. </li></ul><ul><li>Decreases the number of diagnostic (imaging) procedures. </li></ul><ul><li>Diagnoses disease often before it shows up on other tests. </li></ul><ul><li>Shows the progress of disease and how the body responds to treatment. </li></ul><ul><li>Reduces or eliminates ineffective or unnecessary surgical or medical treatments and hospitalization. </li></ul><ul><li>Significantly reduces multiple medical costs and avoids needless pain to the patient. </li></ul>
  75. 85. The influence of blood glucose levels on 18FDG uptake in cancer (Crippa et al. Tumori 1997:83:748-752) <ul><li>8 patients - 20 liver metastases on CT </li></ul><ul><li>PET 1: Fasting (92.4±10.2) </li></ul><ul><ul><li>All 20 were (+) on PET. </li></ul></ul><ul><li>PET 2: Glucose infusion (158±13.8) </li></ul><ul><ul><li>6/20 undetected, and 10 lesions localized less clearly. </li></ul></ul>
  76. 86. <ul><li>70-years-old female smoker </li></ul><ul><li>CT showed Rt mid lung mass and inhomogeneity throughout the liver </li></ul>
  77. 88. Coronal Sagittal
  78. 89. 55 y/o woman Dx’ed with colon ca. S/P resection 2 yrs ago CEA level is rising No evidence of recurrence. CT: normal .

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