Uso do PET no acompanhamento e na detecção de metástases do Câncer de Tireóide. CBAEM Aracajú,2005

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1 Uso do PET no acompanhamento e na detecção de metástases do Câncer de Tireóide CBAEM Aracajú,2005

2 POSITRON EMISSION TOMOGRAPHY

3 Decaímento de Positron + positron (e + ) + 18 F 18 O 18 F 18 O + e + + ν + Energy 18 F decai por emissão de positrons

4 Positron Annihilation 511 kev γ e kev γ

6 SISTEMAS DE DETECÇÃO ET Hybrid PET/SPECT Sensitivity SPECT (collimated detec

7 Radioisótopos

9 FDG Principles : Increased glucose metabolism as universal sign of malignant disease Glucose transporter proteins (GLUT-1) Hexoquinase Glucose 6-phosphat FDG FDG 6-phosphat6

10 Rationale of PET with FDG Glucose transporter in malignant cells up-regulated Phosphorylation (hexokinase) ) in malignant cells is activated Decrease of FDGlucose-6-phosphatase FDG in tumor cells

11 Rationale of PET with FDG - Increase FDG in tumor cells - Quantification of metabolic activity (SUV - High image contrast, excellent spatial resolution. - Applicable without hormone withdrawal.

12 Why use PET in the follow up of Thyroid cancer?

15 ossible reasons : mutation and/or selection of odine negative tumor cells due to RI-therapy When is Pet Indicated in patients with thyroid carcinoma? Measurable Thyroglobulin serum levels without detection of radioiodine accumulating tissue (after complete ablation of thyroid) ) = TG +, PCI - ecurrences of DCT have often lost the ability to oncentrate radioiodine (RI), while increasead lucose metabolism is present.

Measurable Thyroglobulin serum levels without detection of radioiodine accumulating tissue (after

16 When is Pet Indicated in patients with thyroid carcinoma? igh risk patients G or very low, anti-tg tg CI I Recurrences of DCT have often lost the ability t concentrate radioiodine (RI) and to produce TG.

17 CI - Rx Tórax + PCI -, Tg + / PET a, Fem, Ca Pap - Meta pulmonar e óssea - 2 doses de RAI - PCI, Tg + -Rx Tórax+ - PET + Metas Múltiplas PET + Wang, W. et al. J Clin Endocrinol Metab 1999;84:

18 Wang, W. et al. J Clin Endocrinol Metab 1999;84: PCI Tg + / PET a, fem, Ca pap -RX Tórax + - PCI pós 250 mci - PET + Tumor paratraquea - Cirurgia Ca Folicular

PCI Tg + / PET + - 68 a, fem, Ca pap -RX

20 PCI -, Tg =1, anti-tg + / PET + I - PET + CT + PCI Pós dose a, masc, Ca P - PCI Pós ablaçã -Tg= 1, anti-tg + - PET + Pulmão -CT mci -PCI Pós dose - Remoção cirúrgi Wang, W. et al. J Clin Endocrinol Metab 1999;84:

+ - PET + Pulmão -CT + -300 mci -PCI Pós dose - Remoção

21 When is Pet Indicated in patients with thyroid carcinoma? When you want to find lesions that can be surgically resected or stabilized ( Radiation or embolized ) in residual or recurrent disease. - In high risk patients - When markers are + - When other imaging methods have failed

22 Coronal Transaxial

23 75 a, fem, Ca papilífero, Tg +, PCI -, dor torácica PET +, RM + Cirurgia PCI Coronal PET Sagital RM Sagital

24 49 a, masc, pt2bn0m0 PCI neg, Tg +, PET + Cirurgia PET -

25 57 a, fem, pt4bn1mx, 2 PCI PET + Cirurgia PET + Radioterapia PET +

27 PCI PET

28 Accuracy of FDG PET in Thyroid Carcinomas ~ 70% ependent of the degree of dedifferentiation The more malignant, the more FDG uptake)

29 PET / Falso Positivo - 77 a, masc, Ca papilífero -Tg+, PCI pósablação - PET Lesão úmero E - RAI=123 mci - PCI pós dose = Negativa -Bx = Displasia fibrosa -Tg -, Foco desconhecido Wang, W. et al. J Clin Endocrinol Metab 1999;84:

30 Wang, W. et al. J Clin Endocrinol Metab 1999;84: CT + PCI + PET / Falso Positivo - 54 a, Fem, Ca pap -Tiroidect sem ablação - CT + em Pulmão - PCI + em Leito tiroide -Ablação - PCI - Pós ablação -PET + - Biópsia = Granuloma

31 PET / Falso Negativo PCI - PET - PCI pós dose -42 a, Fem, Ca Pa -TG + pós ablação - PCI e PET negat mci -PCI +

32 Wang, W. et al. J Clin Endocrinol Metab 1999;84: PCI - PET - PET / Falso Negativo - 45 a, Fem, Ca pap -Tg+, anti-tg+ -PCI e PET - - US cervical + - PCI + Pós 200 mci

33 etter Pet accuracy with high TSH

34 Relationship between TSH and FDG Uptake by Thyroid Cells TSH activates (indirectly) glucose transport Sisson et al, JCEM 1993 Thus, higher accumulation of FDG in thyroid cancer cells could be expected in case of an elevated serum TSH.

35 FDG PET in DTC under Endogenous TSH (PET under suppression x PET Hypothyroisis) og et al (J Nucl Med 2000 Dec; 41(12): ) 95) erly patients with known metastatic disease 10 (7 fol,, 3 pap), 17 lesions T in euthyrosis (TSH ) vs.. PET in hypothyrosis (TSH ): rease of 63, 1% uptake in tumor lesions (TBR) n Tol et al ( (Thyroid,, 2002 May; ; 12(5):381-7) unger patients with suspicious recurrence 8 (2 fol,, 6 pap) tter ter results (5/8) under endogenous TSH-simulation pared to supression

36 Hypothesis Exogenous TSH stimulation (rh TSH) s hormone medication might cause maximal ivation of FDG uptake by thyroid carcinoma cells

37 Hannover Study ients: n=30 (19w, 11m) DTC s: years tology: 21 pap,, 9 fol M/Stage pt1a N0 M0 pt4b pn1b pm1 / I-IVI IV uspicion of tumor because of: Thyroglobulin levels: increased borderline MIBI-Scan, radioiodine scan, morphology negative or equivocal -Serum glucose level: : normal (Exclusion( of diabetes patients) Petrich T, Eur J Nucl Med Mol,2002

38 FDG-PET in euthyrosis with and without recombinant TSH Timetable Continuing T4 - medication (1) Bq.v. 1-2 meses 0.9 mg Thyrogen 0.9 mg Thyrogen PET (2) 400 MBq FDG I.v MBq I 131 Scan (48h) Scan (optio day H Tg/TSH Tg/TSH Tg/TSH

39 Results Under suppression: PET + 9/30 After rh TSH : PET + 19/30

40 Impact on therapy Follow-up FDG-PET with rh TSH After tumor detection: Change of therapy: 17/19 Pat 7 OP 2 RIT 3 RIT/rediff 5 Rediff No change 2 Without tumor detection: 0

41 Citation Pts Change in SUV notes when TSH high isson et al CEM 77: 1090, Increased Hypothyroid ang et al CEM 84: 2291, % increase rhtsh oog et al Nuc Med 41: 1989, % increase Hypothyroid an Tol et al hyroid 12:381, Increased etrich et al jnm 29:641, % increase hin et al CEM 89:91, % increase Hypothyroid rhtsh rhtsh

42 Well and less differentiated cancer cells may be present in the same patient PCI PET Combination of WBS + PET + rh TSH

43 ll and less differentiated cancer cells may sent in the same patient ombination of WBS and PET after hormone withdrawl or aft ntramuscular injection of recombinant human TSH - Increase in the detection rate to more than 90 % - May change therapeutic startegy in 50 % of the cases Lind P, Acta med Austriaca,2003, 17-2

44 Better Pet accuracy with better machines?

45 PET-CT I124-Iodide Iodide PET / CT in Thyroid Cancer Registered / Fused Transverse Images Courtesy of Dr. Steven M Larson, MSKCC

46 PET for Prognosis

47 G-PET scan can identify high risk subsets in pati h metastasis : Prognostic Value Wang W, JCEM 2000, patients - 41 month of follow up TG and WBS PET Of PET + Patients h rates of uptake High volume of FDG-av Disease ( > 125 ml) < years survival probability

48 Pet uptake x Survival FDG - 3/179 deaths 0.50 (p < 0.25 Median survival = 53 mo FDG + 93/221 deaths Months

49 SUV = SUV= 0 - SUV= 7.3- SUV> 13 SUV x Survival SUV= Months

50 PET and Thyroid Incidentalomas

51 PET INCIDENTALOMAS Patients were refered to the endocrine department because thyroid hot spots on Pet scans US + FNA Indication for surgery in 7 2 Medullary cancer 3 Papillary 2 with capsule invasion 2 Follicular adenoma Van den Bruel, JCEM , 2

52 Conclusions DG-PET uptake in residual/recurrent thyroid a marker of biologic tumor behavior which rrelates with tumor aggressiveness. DG uptake appears to be a better marker of mor aggressiveness than Tg which ca be low in mors which have undergone dedifferentiation.

53 Conclusions t may be helpful in some patients by showing ite of cancer which had not been identified by ther imaging tests et is not infallible in this group of patients: b alse positive and false negative may occur. ET scan is not required and not recommended or routine follow up.

54 Conclusions For DTC tumor imaging FDG-PET appears to be usef in hypothyroidism (or after administration of rh TS in euthyrodism) ) in combination with WBS. Injection of Thyrogen (0.9mg I.M.) on day prior FDG-PET Fasting for 12 hours prior to PET If necessary, normalization of serum glucose levels.

Update on thyroid cancer surveillance and management of recurrent disease. Minimally invasive thyroid surgery

Update on thyroid cancer surveillance and management of recurrent disease Minimally invasive thyroid surgery July 2006 Michael W. Yeh, MD Program Director, Endocrine Surgery Assistant Professor, David