1. در مرکز پزشکی هسته ای دکتر دباغ – دکتر صادقی در خدمت شما هستیم مشهد، ملاصدرا 11 ، پلاک 1/4 www.DSNMC.ir Tel:+98(51) 38411524; +98(51)38472927

2. www.mums.ac.ir/nmrc Nuclear Medicine In Oncology (Brief) V. R. Dabbagh Kakhki, M.D. Nuclear Medicine Specialist Associate Professor DSNMC Nuclear Medicine Research Center (NMRC; MUMS) www.DSNMC.ir

3. Nuclear Medicine Basic Bone ? Tumoral agents CNS and…..

4. SPECT Bone Scan + SPECT Ga- 67 Scan + SPECT Tc99m-RBC Liver Scan + SPECT Tc99m –MIBI Brain SPECT Tl-201 Brain SPECT DMSA(V) Scan + SPECT

5. Oncology: Nuclear Medicine Diagnosis Specific or non-specific Staging Important for proper therapy Response to Therapy Follow-up Early detection of recurrens Treatment Specific or non-specific

6. Diagnostic radiopharmaceuticals Non-specific agents PET or PET-CT F-18 FDG-PET Planar, SPECT or SPECT-CT Diphosphonates – bone scan Ga-67 citrate MIBI Tl-201 DMSA(V)

7. Diagnostic radiopharmaceuticals Specific – binds directly to special tumor antigens or receptors or are accumulated by special metabolic pathway Specific – binds directly to special tumor antigens or receptors or are accumulated by special metabolic pathway PET or PET/CT - no commercially available PET or PET/CT - no commercially available 11 C-HED 11 C-HED Planar, SPECT or SPECT/CT Planar, SPECT or SPECT/CT MIBG MIBG I-131 I-131 111 In/Tc99m- Octreotide 111 In/Tc99m- Octreotide MoAb : labelled with In-111, I-123/131 or Tc-99m MoAb : labelled with In-111, I-123/131 or Tc-99m

8. Bone Scan 99mTc -MDP

9. Bone Scan Clinical applications Clinical applications Bone metastases, Bone metastases, Primary bone tumors, Primary bone tumors, Trauma and fractures, Stress fractures, Trauma and fractures, Stress fractures, Osteonecrosis, Osteonecrosis, osteomyelitis, osteomyelitis, Prosthesis evaluation, Prosthesis evaluation, Metabolic bone disease, Metabolic bone disease, Arthritis, Arthritis, Sensitive But not Specific

10. Bone scan Scan pattern Scan pattern Increased Uptake Increased Uptake Defect - cold lesion Defect - cold lesion Flare phenomenon – Increased uptake and number of lesions in the case of effective therapy Flare phenomenon – Increased uptake and number of lesions in the case of effective therapy Super-scan (spread malignancies) - diffusely increased uptake Super-scan (spread malignancies) - diffusely increased uptake

12. Rib Fractures

13. Osteosarcoma Osteosarcoma A 16-year-old boy with pain in the upper left tibia diagnosed as primary osteogenic sarcoma of the left femur Bone scan reveals disseminated bone and lung metastases.

15. Bone scan – multiple metastases

16. Lung cancer – cold lesion

17. Bone scan - prostate cancer progression

18. Bone Metastases Superscan: Disseminated bone metastases secondary to prostatic cancer

19. Bone Scan PRIMARY MALIGNANT BONE DISEASE Osteosarcoma Osteosarcoma Ewing Sarcoma Ewing Sarcoma Chondrosarcoma Chondrosarcoma Multiple Myeloma Multiple Myeloma Rhabdomyosarcoma Rhabdomyosarcoma Assessment of extension of the lesions or metastatic involvement

20. Ewing Sarcoma

21. Ga-67 scan Clinical indications Clinical indications Lymphoma Lymphoma staging and monitoring effect of therapy staging and monitoring effect of therapy Melanoma Melanoma Lung cancer Lung cancer Hepatoma Hepatoma Ccombination with other imaging modalities (SPECT/CT)

22. Ga-67; a cornerstone in functional imaging of lymphoma Role; Diagnostic and prognostic data Staging Monitoring response to treatment Differentiate between fibrotic or necrotic tissues from viable lymphoma in a residual mass Early diagnosis of recurrence Predicting outcome 18 F-FDG PET; gradually replacing GS

23. Gallium Scan SPECT A baseline examination before treatment A baseline examination before treatment intense Ga avidity: small, non-cleaved cell lymphoma (lesion sens:89%) intense Ga avidity: small, non-cleaved cell lymphoma (lesion sens:89%)

24. Clinical History: 20-year-old, three weeks post partum with anterior mediastinal mass. Findings: Gallium scan at shows mediastinal adenopathy and bilateral breast uptake. Diagnosis: Hodgkin's Lymphoma.The breast uptake represents benign uptake secondary to lactation.

25. Ga-SPECT/CT in a patient with showing a residual mass on CT after treatment. Abnormal 67 Ga uptake is demonstrated in the corresponding residual CT abnormality, indicating the presence of residual viable tumor tissue

26. Baseline GS GS after one cycle of chemotherapy Rapid Response to treatment

27. Tl-201 and Tc99-MIBI Brain Tumors Brain Tumors Sarcoma Sarcoma Breast Imaging Breast Imaging

28. Mitochondria Nucleus MIBI ΔΨm ΔΨc 99mTc Passive diffusion + + + + + - - - - - - - - -

29. Mitochondria Nucleus MIBI ΔΨm ΔΨc 99mTc Passive diffusion + + + + + - - - - - - - - - MDR Proteins Active Efflux

30. Brain Tumors F-18 FDG PET Grading F-18 FDG PET Grading Prognosis Prognosis Tumor recurrence Tumor recurrence Tl-201 Radiation necrosis Tl-201 Radiation necrosis Tumor viability Tumor viability Tc99m Sestamibi (choroid plexus uptake) Tc99m Sestamibi (choroid plexus uptake) SPECT

31. Brain tumor

34. FDG PET – brain tumor post th two foci on CT, only one viable tumor

35. earlylate Parathyroid Scan: Tc99m-MIBI Scan + SPECT Parathyroid adenoma

36. Specific methods Binding to receptors or antigens Binding to receptors or antigens MIBG – pheochromocytoma, neuroblastoma in children MIBG – pheochromocytoma, neuroblastoma in children Octreoscan – neuroendocrine tumors Octreoscan – neuroendocrine tumors I-131 – thyroid cancer – follow-up and treatment I-131 – thyroid cancer – follow-up and treatment

37. MIBG SCINTIGRAPHY

38. MIBG: Clinical application Adrenal medullary hyperplasia Adrenal medullary hyperplasia Pheochromocytoma: 90% sensitive and even more specific(95-99%) Pheochromocytoma: 90% sensitive and even more specific(95-99%) Paragangliomas Paragangliomas It can show metastatic lesions very effectively It can show metastatic lesions very effectively Neuroblastoma Neuroblastoma

41. 11 C- Hydroxyephedrine similar to MIBG

42. SPECT/CT carcinoid SPECT/CT carcinoid OctreoScan+ SPECT

43. PET in oncology: General aspects( 18 FDG) Cell membrane 18 FDGGlucose 18 FDGGlucose hexokinase 18 FDG-6-PGlucose-6-P Metabolites of Glucose

44. FDG PET For several tumors For several tumors Mainly lymphomas, lung cancers, melanoma, colorectal cancers and others Mainly lymphomas, lung cancers, melanoma, colorectal cancers and others Not suitable for prostate cancer Not suitable for prostate cancer At least 1 w post chemo, 3 m radiotherapy At least 1 w post chemo, 3 m radiotherapy

45. PET in oncology: 18 FDG can be used for: 18 FDG can be used for: Focal lesions (malignancy potential) Focal lesions (malignancy potential) Staging Staging Monitoring response to therapy Monitoring response to therapy Prognosis Prognosis Evaluation of tumor recurrence Evaluation of tumor recurrence

46. PET in oncology: Breast cancer (Staging) A 44 year old female with an axillary nodule proved to be carcinoma on biopsy. A FDG PET exam was then performed and revealed extensive metastases to axillary and supraclavicular lymph nodes, as well as the primary lesion in the right breast (black arrow)

47. PET in oncology: Colon cancer (Recurrent cancer) A patient with a history of colon cancer, evaluated for two pulmonary nodules. The FDG PET demonstrated uptake in the pulmonary nodules (not shown) and also revealed diffuse omental metastases

48. PET in oncology: Melanoma (Staging) A 71 year old male with a history of melanoma on the left shoulder.On CT, the abdomen had been interpreted as negative. The FDG PET exam revealed extensive metastatic disease throughout the body.

49. PET------  PET/CT

50. FDG PET Tumor of unknown origin Pharyngeal cancer

51. PET:100 % CT: 0 % Stomach cancer

52. PET: 80 % CT: 20 % Stomach cancer

53. PET: 60 % CT: 40 % Stomach cancer

54. PET: 40 % CT: 60 % Stomach cancer

55. PET: 20 % CT: 80 % Stomach cancer

56. PET: 0 % CT: 100 % Stomach cancer

57. 18 FDG-PET and PET/CT Lung Cancer Solitary pulmonary nodule Solitary pulmonary nodule Diagnosis of primary lung cancer Diagnosis of primary lung cancer Staging Staging Therapy Planning Therapy Planning Monitoring of therapy Monitoring of therapy Detection of recurrence Detection of recurrence Ideal site for possible tissue diagnosis Ideal site for possible tissue diagnosis Prediction of prognosis. Prediction of prognosis. PET/CT has the best of both worlds of metabolic and anatomic imaging and may provide optimal disease assessment. PET/CT has the best of both worlds of metabolic and anatomic imaging and may provide optimal disease assessment.

58. 18 FDG-PET and PET/CT Solitary Pulmonary Nodule The negative predictive power of PET is sufficiently high to avoid biopsy. If FDG-PET is negative for lesions > 7 mm diameter, then the process is most likely benign, and may be followed with serial surveillance. When FDG-PET is positive then diagnostic and definitive treatment may be instituted

59. PET/CT :more useful than PET in determining the T stage and in assessing the presence of mediastinal or chest wall invasion PET was significantly more accurate than CT or MRI in identifying nodal metastasis with An accuracy of 81% to 96% PET/CT : even higher diagnostic accuracy than either CT or PET alone with a sensitivity of 89% and specificity of 94% and an overall diagnostic accuracy of 93%.

60. 18 FDG-PET & PET/CT LC Staging: Distant Metastasis (M) In brain and genitourinary system, PET is less accurate in identifying malignancy. In brain and genitourinary system, PET is less accurate in identifying malignancy. As the brain is common site for metastatic lung cancer, CT or MRI recommended. As the brain is common site for metastatic lung cancer, CT or MRI recommended.

61. PET in oncology: Bronchogenic carcinoma (Staging) A patient had a left lung NSCLC. There was no uptake of tracer within the hila or mediastinum to suggest nodal metastases, however, unsuspected bone metastases were found in the right humerus and right hip (black arrows).

62. PET in oncology: Bronchogenic carcinoma (Staging) Uptake within the patients primary lung cancer can be seen within the right chest. Uptake within the bilateral adrenal glands (black arrows) confirmed the presence of adrenal metastases.

63. HL and a negative initial BMB but pathological focal marrow FDG uptake in the mid- and lower lumbar spine, sacrum and left ischium (arrows).

64. A grade 3 follicular lymphoma and a negative initial bone marrow biopsy of the iliac crest. PET slices show pathological marrow uptake in the sternum (small arrows). which was confirmed histologically. There is also lymph node involvement of the right hilum (large arrow).

65. GS in a patient with high grade NHL and BM transplantation. He presented with a palpable spleen, fever, dyspnea and pancytopenia. The MRI showed findings most consistent with multiple peripheral splenic infarcts, increasing splenomegaly and no change in multiple small retroperitoneal LNs.

67. Complete response and good prognosis of HL. (A)Baseline PET: Abnormal FDG uptake in sites of lymphadenopathy in the left supra- clavicular region, the right axilla, the mediastinum bilaterally, the left lung hilum, and the porta hepatis region. (B)Repeat FDG-PET, performed after one cycle of chemotherapy, is negative.

68. NHL: Assessment of partial response, prediction of poor outcome, and detection of recurrence. (A)Baseline : multiple areas of abnormal FDG uptake in sites of mesenteric and retroperitoneal adenopathy. (B) Repeat FDG-PET performed after two cycles of chemotherapy shows residual but less prominent abnormal FDG uptake in abdominal sites indicating partial response. (C)FDG-PET at the end of treatment is negative indicating that complete response was achieved. (D)Routine follow-up FDG-PET at 4 months of remission shows recurrent disease inabdominal sites.

69. Stage IIA high-grade NHL. Baseline:Highly hypermetabolic lymph nodes in the left axillary and cervical areas PET performed after 3 courses of chemotherapy shows a complete metabolic response. The patient is in complete clinical remission 6 months after completing the treatment.

70. HD : A: Baseline FDG PET:Multiple foci of increased activity in cervical and mediastinal areas as well as right hilar and lung infiltration. B: FDG PET performed after 2 cycles of polychemotherapy indicates residual 18F-FDG uptake in a right cervical lymph node. C: Treatment failure was observed at the end of treatment.

71. Lymphoma (Residual mass post-therapy) A patient received chemotherapy for lymphoma. There was a residual left neck mass following completion of therapy. A FDG PET exam revealed persistent metabolic activity within the mass concerning for residual tumor.

72. FDG-PET or PET/CT at diagnosis Negative No more follow-up scans Positive Repeat PET or PET/CT during therapy Positive scan HD and NHL Negative scan, NHL,HD stage ΙΙΙ and ΙV Negative scan HD stage Ι and ΙΙ Consider more aggressive therapy 1 year follow-up scans mandatory Follow-up scans only within clinical suspicion Repeat scan after secondary treatment and before transplantation Negative: Further installed treatment and repeat scan at the end of therapy