1. Carcinoma scarsamente differenziato Terapia radiorecettoriale
Neoplasie della tiroide
Carcinoma scarsamente differenziato
Terapia radiorecettoriale
Annibale Versari Medicina Nucleare – Centro PET AO Arcispedale S.Maria Nuova - IRCCS Reggio Emilia
15 giugno
2011 1

2. Background
Metastases from differentiated thyroid carcinoma (DTC) can lose in time the capacity to concentrate radioiodine and the possibility to have a specific treatment.

3. Background
DTC may express somatostatin receptors; this offers a further opportunity of diagnosis and treatment.
Tenenbaum F et al J Nucl Med 1995
Görges R et al Nuklearmedizine 1999
Forssell-Aronsson EB et al J Nucl Med 2000

4. Nuclear Medicine Imaging
Target site:
Somatostatin receptors
Somatostatin analogs
Scintigraphy, SPECT, SPECT/CT
111In-Octreoscan
PET/CT
68Ga-DOTATOC
68Ga-DOTANOC
68Ga-DOTATATE

7. Physics properties (LET)β-
(Mev) γ
(Kev)
T1/2
(days)
177Lu
0.49
6.7
90Y
2.27
2.7
mean range in body tissue
177Lu mm
90Y mm

9. Results

10. JJJ Teunissen et al
J Nucl Med 2005

11. JJJ Teunissen et al
J Nucl Med 2005

12. 68Ga DOTATOC PET/CT
68Ge/68Ga Generator

13. 68Ge/68Ga Generator EC 68Ge (t1/2 : 270.8 d) 68Ga (t1/2 : 68 m)
68Ga emissions
b E(max) = 1.9 MeV %
electron capture %

14. Ant Lat

15. Metastatic differentiated thyroid cancer negative at radioiodine scan
B.M. male, 75 year old 68Ga-DOTATOC PET/CT:
Diffuse lung metastases (+ bone and lymph node mts)

17. Metastatic differentiated thyroid cancer negative at radioiodine scan
P.M. female, 61 year old
68Ga-DOTATOC PET/CT: multiple bone metastases

18. Patients Results Negative PET: 23 pts (51%) Positive PET: 22 pts (49%)
45 pts with non-radioiodine-avid DTC, metastatic or suspicious metastatic underwent
68Ga-DOTATOC PET/CT
m/f 21/24
age yrs,
mean 59
Results
Negative PET: 23 pts (51%)
Positive PET: 22 pts (49%)

19. Results
Multivariate analysis does not show any significant association with a positive 68Ga-DOTATOC PET/CT

20. From Diagnosis to Treatment
68Ga
DOTATOC
Treatment
90Y / 177Lu

21. Results
13/45 (28%) patients satisfied the criteria (high uptake in the lesions) to access PRRT with 90Y/177Lu-DOTATOC
11 pts underwent treatment (90Y: 9 pts - 177Lu: 2 pts)

22. 90Y-DOTATOC
90Ittrium

23. Radiolabelled Somatostatin Analogs Therapy

24. 90Y/177Lu-DOTATOC Treatment
pts
Cumulative Dose
(GBq)
Cycles
Interval (weeks)
Dosimetry
90 Y 9
5-15
2-6
8-12
111In-DOTATOC
177Lu 2
15-22
3-4
7-10

25. Patient evaluation PET VCAR RECIST evaluation 68Ga-PET/CT evaluation
functional volume
SUV
tumor/muscle SUV
PET VCAR

26. Response to the treatment Follow up: 6-15 months
RECIST Response
SUV max Response PR SD PD
Patients (11) 2 4
4 (1 NA) 5
Lesions
Lymph node (23)
18%
78% 4%
34%
52%
14%
Bone (130) NA
27%
33%
40%
Lung (20) 5%
90%
39%
36%
25%
PR - partial response
SD - stable disease
PD - progression disease
According to EORTC
criteria modified by our
Ethics Committee

27. Severe dyspnea No dyspnea
O2-therapy: 6-7 hours/day No O2-therapy
Before therapy
After 4 cycles
90Y-DOTATOC
(cumulative dose 268 mCi)
Sept 2007
Mar 2009
B.M. male, 75 year old

28. B.M. male, 75 year old

29. Pre-therapy Post-therapy
P.M. female, 61 year old

30. Pre-therapy Post-therapy
P.M. female, 61 year old

31. pain no pain no pain pain
Treatment steps
P.M. female, 61 year old

32. pain no pain no pain pain
Tumor/muscle SUV
Treatment steps
P.M. female, 61 year old

33. Tireoglobulin in comparison with treatment response
Patient
Tg pre-treatment
Tg post- treatment
68Ga-PET
SUV
RECIST 1
>1000
stable PR 2
300 PD 3
0.5 4
<0.3 SD 5
>6000 6
380
increased 7
7500 8
385 9
0.4 10
227 11
PR - partial response SD - stable disease PD - progression disease

34. Results
The clinical response is superior to the PET/CT findings.

35. Side effects Nausea (grade 1): 4/11 Astenia (grade 1): 2/11
Hematologic Toxicity: 4/11
(transient decreasing of platelets, WBC, eritrocytes)
Renal failure: 1/11

36. Side effects Impact on renal function

37. Side effects Impact on blood platelets

38. Side effects Impact on WBC

39. Conclusions
Labelled somatostatin analogs are very interesting for pts with progressive radioiodine-negative Differentiated Tyroid Cancer
About 50% of these pts are positive at 68Ga-DOTATOC PET/CT
The possibility to use the same peptide for therapy in PET positive pts is promising but needs further confirmation in larger number of pts.

40. Grazie per l’attenzione
Ponte di Calatrava
Reggio Emilia