1. TUMOR IMAGING MUDr. Kateřina Táborská

2. 1.Differentiation of benign from malignant lessions 2.Staging of malignant disease 3.Differentiation of reccurent malignant disease from therapy induced changes 4.Monitoring the response to therapy Objectives of Tumor Imaging

3. AGENTS Choise depends on: Mechanism of uptake Sensitivity for detection of malignant lesion Specificity of uptake Sites of normal physiological uptake in the body and routes of excretion availability

4. Radiopharmaceuticals Nonspecific affinity for neoplastic tissue, may be used to image a range of tumors in various organs 18 F Fluorodeoxyglucose 67 Gallium citrate 201 Thallium 99m Tc sestamibi Designed to label specific tumor antigens, receptors 111 In Octreoscan 123 I MIBG 123/131 I NaI

5. Positron Emission Tomography Is rapidly becoming a major diagnostic modality similar to conventional NM in principle, but it uses diferent radiopharmaceuticals + more complex acquisitions method – better resolution based on coincidence detection of two gamma rays (511 keV) that originate from annihilation of positron – electron pair

6. PET radiopharmaceuticals contain short half-life radionuclides (prepared in cyclotron), that decay, emitting positrons Radionuclid half- life ( mins ) RPH metabolic pathway 18 F 110 18 F-FDG glucose metabolism 11 C 20 11 C-methioninprotein syntesis 13 N 10 13 NH 3 blood flow 15 O 2 15 O - H 2 Oblood flow

7. 18 FDG tracer of glucose metabolism Estimate the rate of glucose utiliation bloodcell x  greater number of Glucose transporter proteins  Elevated levels of intracellular enzymes that support glycolysis x Tumor cells demonstrate glucose metabolism

8. Physiological distribution of 18 FDG brain myocardium bowel liver spleen excreted by the kidneys Inflammation specificity

9. Examination 1.Patient preparation 6 hours fasting, good hydration 2.Check blood glucose level-lower than 8,3 mmol/l 3.RP administration – iv. 4.Accumuation phase – 60 - 90 minuts 5.Whole body scanning 5-7 bed position, emission, transmission (CT) 6.Data processing 7.Evaluation Contraindicaton pregnancy, hyperglycaemia, inability to lie without movement during acquisition

10. Oncology Lung cancer Head and neck cancer Colorectal cancer Esophageal cancer Lymphoma Melanoma Breast cancer Thyroid cancer Cervical cancer Pancreatic cancer Brain tumor

11. Differentiation of benign from malignant lessions SOLITARY PULMONARY NODULE ( about a third of SPN in patients older than 35yr malignant) chest x-raymetabolism of FDG CT sputum cytology+- bronchoscopy mediastinum percutaneous needle biopsydistant metastases mediastinoscopy open lung biopsy Sensitivity 95%, specificity 80% (CT sensitivity 100%, specificity 50%)

12. Differentiation of benign from malignant lessions SOLITARY PULMONARY NODULE

13. - Weight lost (15 kg) - CT and endoultrasound suspicion of malignancy - high risk patient undergoing dialysis - PET negative - clinical follow up without progression Differentiation of benign from malignant lessions

14. Staging of malignant disease is essential for treatment (surgery, chemotherapy) Functional changes preceed anatomical N,M morpologic imaging is less accurate dependent on the size - 1 cm in thorax, 1-2 cm abdomen

15. Staging of malignant disease : lung cancer According to CT T2N0M0 Dision operation According to PET T2N0M1 Dision chemotheraphy

16. Differentiation of reccurent malignant disease from therapy induced changes MRI18FDG MRI : metastases of lung Ca – frontal region - necrosis? FDG: frontal region ametabolism (necrosis), occipital region hypermetabolism

17. Differentiation of reccurent malignant disease from therapy induced changes Hodgkin‘s lymphoma, KS II A (bulky mediastinum, neck restaging after 2. cycle of chemotherapy

18. Monitoring the response to therapy Hodgkin‘s lymphoma before treatmentafter treatment

19. 67 Ga citrate lymphoma labeled monoclonal antibody (OncoScint, CEA scan) colorectal, ovarian cancer 99m Tc MIBI, TETROFOSMIN, DMSA(V) thyroid Ca ALTERNATIVES

20. thyroid Ca 99mTc MIBI

21. 99mTc MIBI – parathyroid adenoma Dual-phase scan Accumulation by thyroid and parathyroid tissue in proportion to blood flow and metabolic rate Activity in normal parathyroid glands is too low to be seen on image, abnormal uptake > 300 mg Wash out of normal thyroid tissue is faster than from abnormal parathyroid adenomas and hyperplasia

22. 99mTc MIBI – parathyroid adenoma Dual-phase scan iv. Early images (10-15 min) delayed images (2 hours)

23. NEUROENDOCRINE TUMORS Derived from pluripotent stem cells or differentiated neuroendocrine cells capacity to synthesize hormones/ peptide neurotransmitters biogenic amine precursor uptake and decarboxylation (APUDomas) intracytoplasmic storage granule on electron microscopy express cell surface receptors for somatostatin

24. NEUROENDOCRINE TUMORS paragangioma neuroblastoma pheochromocytoma (catecholamine) carcinoid (serotonin and metabolites) medullary thyroid cancer (calcitonin)

25. NEUROENDOCRINE TUMORS localisation, characterisation 123 I 123 I MIBG 111 In OCTREOSCAN therapy 131 I MIBG

26. 123 I-, 131 I- METAJODBENZYLGUANIDIN 123 I T1/2 13 hours, γ rays 27, 159, 529 keV 131 I T ½ 8,04 days, β, γ rays structurally resembles norepinephrine accumulation in cytoplasmic catecholamine storage granules adrenal medulla, sympathetic nervous tissue t umor cells that posses the type-1 amine uptake mechanism

27. 123 I-, 131 I- METAJODBENZYLGUANIDIN

28. SENSITIVITY: Feochromocytoma80-90 % Carcinoid50-60 % Paraganglioma40-60 % MTC 30 %

29. 123 I-, 131 I- METAJODBENZYLGUANIDIN Preparation: to minimize thyroid uptake (KI, Lugol‘s solution) Stop drugs that interfere with MIBG uptake ( catecholamine agonist) Imaging: 24 h after iv. medullary thyroid ca

30. 111 In-OCTREOSCAN ® Pentetreotid - somatostatin analog Somatostatin - neuropeptide (first found in the hypothalamus) high density of somatostatin receptors NT, astrocytoma, meningeoma, breast ca, lymphoma γ 111 In T ½ 67h, (γ rays 171, 245keV )

31. 111 In-OCTREOSCAN ® SENZITIVITY: Glukagonom100 % Vipom 88 % Gastrinom 73 % Nesekreční GEP 82 % Feochromocytom > 85 % Karcinoid 86 – 96 % MTC 65 – 70 % Malubuněčný Ca plic 80 – 100 % Inzulinom 46 % www.snm.org, guideline, II/2001

32. 111 In-OCTREOSCAN ® Imaging : 4-6h, 24 h after iv. carcinoid

33. SENTINEL LYMPH NODE DETECTION First node in a lymph node bed to which a tumor cell would come if it penetrated into lymphatic fluid If an sentinel node is tumor free, with 97-98% accuracy, there is no tumor spread to any lymph node

34. SENTINEL LYMPH NODE DETECTION STAGING PROGNOSIS breast prostate cervix, vulva melanoma

35. SENTINEL LYMPH NODE DETECTION Radiopharmaceuticals 99mTc albumin colloids (Senti-Scint ® 100-600 nm) EXAMINATION: on the morning of surgery (1 day before) aplication subdermal intratumoral peritomoral

36. SENTINEL LYMPH NODE DETECTION EXAMINATION: Imaging, marked on skin In the operating room – hand held gamma detecting probe (combination with blue dye)

37. CONCLUSION ADVANTAGES functional information DISADVANTAGES lack of anatomic precise localisation SOLUTION SPECT/CT PET/CT