1. Radionuclide methods in oncology Otto Lang, MD, PhD Otakar Bělohlávek, MD, CSc Dept Nucl Med Charles Univ, 3rd Med Fac Materials for medical students

2. Role for Nuclear Medicine Diagnosis Diagnosis Specific or non-specific Specific or non-specific Staging Staging Important for proper therapy Important for proper therapy Follow-up Follow-up Early detection of recurrens Early detection of recurrens Treatment Treatment Specific or non-specific Specific or non-specific

3. Tumors Metabolically active tissues – many similar properties as inflammation Metabolically active tissues – many similar properties as inflammation Increased vascularization Increased vascularization Increased capillary permeability Increased capillary permeability Newly proliferated capillaries Newly proliferated capillaries Increased blood flow Increased blood flow Metabolically active cells Metabolically active cells Increased energy demand Increased energy demand

4. Tumor cells High density of some common receptors High density of some common receptors Expression of several specific receptors Expression of several specific receptors Expression of some specific tumor antigenes Expression of some specific tumor antigenes All these properties could be used for imaging and therapy All these properties could be used for imaging and therapy

5. Diagnostic radiopharmaceuticals Non-specific - demonstrate tumor sites but are not specific for malignancy Non-specific - demonstrate tumor sites but are not specific for malignancy PET or PET-CT PET or PET-CT F-18 FDG – anaerobic metabolism F-18 FDG – anaerobic metabolism Planar, SPECT or SPECT-CT Planar, SPECT or SPECT-CT Diphosphonates – bone scan Diphosphonates – bone scan Ga-67 citrate – similar to FDG – localising agent Ga-67 citrate – similar to FDG – localising agent Colloids – liver-spleen scan Colloids – liver-spleen scan Leukocytes – bone marrow scan Leukocytes – bone marrow scan MIBI – several tumors MIBI – several tumors

6. 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 Planar, SPECT or SPECT/CT Planar, SPECT or SPECT/CT I-123/131 MIBG for neuroendocrine tumours I-123/131 MIBG for neuroendocrine tumours I-131 for differentiated thyroid carcinomas I-131 for differentiated thyroid carcinomas In-111 octreotide for tumours expressing somatostatin receptors. In-111 octreotide for tumours expressing somatostatin receptors. monoclonal antibodies labelled with In-111, I-123/131 or Tc-99m monoclonal antibodies labelled with In-111, I-123/131 or Tc-99m

7. Therapeutic radiopharmaceuticals Non-specific Non-specific Sr-89, Sm-153, Re-189 Sr-89, Sm-153, Re-189 Bone pain palliation Bone pain palliation Specific Specific I-131 I-131 Thyroid cancer, as specific diagnostic if tumor significantly accumulates Thyroid cancer, as specific diagnostic if tumor significantly accumulates Y-90 Y-90 Zevalin – monoclonal antibody for B-cell lymphomas Zevalin – monoclonal antibody for B-cell lymphomas

8. Ga-67 scan Introduced in seventies of 20th century for lymphomas (prof. Dienstbier) Introduced in seventies of 20th century for lymphomas (prof. Dienstbier) Mechanisms of accumulation Mechanisms of accumulation tumour viability tumour viability blood flow blood flow capillary permeability capillary permeability lymphatic drainage lymphatic drainage transferrin receptors on the tumour cells transferrin receptors on the tumour cells

9. Ga-67 scan Procedure Procedure Patient preparation Patient preparation Laxatives for bowel preparation post injection, nothing else Laxatives for bowel preparation post injection, nothing else Several weeks post tumor therapy (FN) Several weeks post tumor therapy (FN) radiation therapy and chemotherapy can alter the normal pattern of gallium distribution radiation therapy and chemotherapy can alter the normal pattern of gallium distribution 180 MBq is usually administered 180 MBq is usually administered imaging follows after 48 – 72 hours imaging follows after 48 – 72 hours WB + SPECT, middle-energy collimator WB + SPECT, middle-energy collimator

10. Ga-67 scan Normal scan Normal scan Accumulates in bone marrow and liver. Accumulates in bone marrow and liver. Splenic uptake is variable. Splenic uptake is variable. The kidneys are usually visualized and also lacrimal, salivary, nasopharyngeal and genital activity is often present. The kidneys are usually visualized and also lacrimal, salivary, nasopharyngeal and genital activity is often present. Female breasts can be visualized, but accumulation is physiologically symmetrical. Female breasts can be visualized, but accumulation is physiologically symmetrical. Radioactivity is commonly seen in the colon Radioactivity is commonly seen in the colon

11. 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 Combination with other imaging modalities is necessary (SPECT/CT) Combination with other imaging modalities is necessary (SPECT/CT)

12. Bone scan Radiopharmaceuticals Radiopharmaceuticals Tc-99m MDP, HDP Tc-99m MDP, HDP Tissue accumulation depends on Tissue accumulation depends on blood flow blood flow capillary permeability capillary permeability metabolic activity of osteoblasts and osteoclasts metabolic activity of osteoblasts and osteoclasts mineral turnover mineral turnover 500 to 800 MBq, imaging 2 to 3 hours later – WB + SPECT 500 to 800 MBq, imaging 2 to 3 hours later – WB + SPECT

13. Bone scan Clinical indications: Clinical indications: Diagnosis of metastases of different tumors – staging and follow-up Diagnosis of metastases of different tumors – staging and follow-up Positivity many months before an abnormality can be detected on X ray - method of choice to seek for bone metastases Positivity many months before an abnormality can be detected on X ray - method of choice to seek for bone metastases Mainly Mainly Bronchogenous carcinoma, prostate, breast, thyroid, and renal tumours Bronchogenous carcinoma, prostate, breast, thyroid, and renal tumours

14. Bone scan Scan pattern Scan pattern increased accumulation in the surrounding bone - hot lesion increased accumulation in the surrounding bone - hot lesion defect - cold lesion (some metastases –breast) - rare (very fast grow – no bone reaction) defect - cold lesion (some metastases –breast) - rare (very fast grow – no bone reaction) flare phenomenon – increased number of lesions in the case of effective therapy flare phenomenon – increased number of lesions in the case of effective therapy super-scan (spread malignancies) - diffusely increased uptake super-scan (spread malignancies) - diffusely increased uptake

15. Liver/spleen scan Metastases of GI tumors Metastases of GI tumors Replaced by sono and CT Replaced by sono and CT Scan pattern – cold nodules, different number and size Scan pattern – cold nodules, different number and size Mainly Mainly Colorectal, ovarian, breast, lung, lymphoma Colorectal, ovarian, breast, lung, lymphoma Always poor prognosis Always poor prognosis

16. Thyroid scan Non-specific test with pertechnetate Non-specific test with pertechnetate Mainly cold nodules – especially in children – must be biopsied!!! Mainly cold nodules – especially in children – must be biopsied!!!

17. Bone marrow scan Colloids or leukocytes Colloids or leukocytes Similar as bone scan Similar as bone scan Better sensitivity Better sensitivity

18. FDG PET http://www.homolka.cz/nm/ For several tumors – staging and follow-up For several tumors – staging and follow-up 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 Patient preparation Patient preparation At least 1 w post chemo, 3 m radiotherapy At least 1 w post chemo, 3 m radiotherapy One hour before injection physical rest One hour before injection physical rest Fasting, no milk, no sugar Fasting, no milk, no sugar

19. Specific methods Binding to receptors or antigens Binding to receptors or antigens I-123 MIBG – pheochromocytoma, neuroblastoma in children I-123 MIBG – pheochromocytoma, neuroblastoma in children In-111 Octreoscan – neuroendocrine tumors (insulinoma, vipoma, carcinoid), SCLC In-111 Octreoscan – neuroendocrine tumors (insulinoma, vipoma, carcinoid), SCLC I-131 – thyroid cancer – follow-up and treatment I-131 – thyroid cancer – follow-up and treatment

20. Specific methods Monoclonal antibodies Monoclonal antibodies Anti-CEA – rather in detection of relaps Anti-CEA – rather in detection of relaps In the pelvis better than CT In the pelvis better than CT In the liver CT better In the liver CT better In-111 Oncoscint – colorectal, ovarian In-111 Oncoscint – colorectal, ovarian Melanoma – antibody against melanin Melanoma – antibody against melanin Ga scan is better Ga scan is better

21. Bone scan – multiple metastases

23. Lung cancer – cold lesion

24. Breast cancer normal X ray with hot spot on scintigraphy

25. Superscan – prostate cancer

26. Bone scan - prostate cancer progression

27. Breast cancer – FU – progr.

28. Thyroid – folicular ca on sonography solid nodule

29. Thyroid cancer - anaplastic

30. Thyroid cancer Tc-99mTc-99m post surgery I-131

31. Thyroid cancer –I-131 - meta

32. earlylate Tc-99m sestamibi parathyroid adenoma

33. Neuroblastoma liver and bone involvment Bone scan I-131 MIBG scan

34. Carcinoid – liver meta

36. Ga scan – lung cancer

37. Ga scan - lymphomas

38. Palpable mass on the neck lymphoma Tc-99m pertechnetate Ga-67 citrate

39. SPECT/CT carcinoid SPECT/CT carcinoid

40. SPECT/CT breast cancer

41. SPECT/CT lung cancer

43. FDG PET - normal

44. FDG PET melanoma

45. Metastatic involvment of neck lymph nodes Tumor of unknown origin FDG PET

46. Tumor of unknown origin Pharyngeal cancer

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

48. Staging colorectal CA

49. Effect of therapy Lung cancer

50. Stomach 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. NSCLC CT: T2 N0 Mx ~ stg. IB ?

58. NSCLC CT: T2 N0 Mx ~ stg. IB ? PET: T2 N2 M0 ~ stg. II

59. NSCLC CT: T2 N0 Mx ~ stg. IB ? PET: T2 N2 M0 ~ stg. II PET/CT: T2 N2 M1 ~ stg. IV PET/CT is more than PET and CT