Annibale Versari

Medicina Nucleare – Centro PETAO Arcispedale S.Maria Nuova - IRCCS

Reggio Emilia

versari.annibale@asmn.re.it

  Neoplasie della tiroide

Carcinoma scarsamente differenziato

Terapia radiorecettoriale

15 giugno 2011

Background

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

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

Nuclear Medicine Imaging

Somatostatin analogs

Target site:Somatostatin

receptors

Scintigraphy, SPECT, SPECT/CT • 111In-Octreoscan

PET/CT •68Ga-DOTATOC•68Ga-DOTANOC•68Ga-DOTATATE

Physics properties (LET)

mean range in body tissue

177Lu 0.5-2mm

90Y 3-11 mm

•

•

β- (Mev)

γ (Kev)

T1/2 (days)

177Lu 0.49 110-210 6.7

90Y 2.27 2.7

Results

JJJ Teunissen et alJ Nucl Med 2005

JJJ Teunissen et alJ Nucl Med 2005

68Ga DOTATOC PET/CT

68Ge/68Ga Generator

68Ge/68Ga Generator

68Ge (t1/2 : 270.8 d) 68Ga (t1/2 : 68 m)

EC

68Ga emissions

E(max) = 1.9 MeV 89%

electron capture 11%

Ant Lat

B.M. male, 75 year old 68Ga-DOTATOC PET/CT:Diffuse lung metastases (+ bone and lymph node mts)

Metastatic differentiated thyroid cancer Metastatic differentiated thyroid cancer negative at radioiodine scannegative at radioiodine scan

P.M. female, 61 year old 68Ga-DOTATOC PET/CT: multiple bone metastases

Metastatic differentiated thyroid cancer Metastatic differentiated thyroid cancer negative at radioiodine scannegative at radioiodine scan

Patients45 pts with non-radioiodine-avid DTC, metastatic or

suspicious metastatic underwent 68Ga-DOTATOC PET/CT

m/f 21/24age 23-82 yrs,mean 59 Results

Negative PET: 23 pts (51%)Positive PET: 22 pts (49%)

Results

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

From Diagnosis to Treatment

Diagnosis68Ga

Treatment90Y / 177Lu

DOTATOC

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)

90Y-DOTATOC

90Ittrium

Radiolabelled Somatostatin Analogs Therapy

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 177Lu

PET VCAR

Patient evaluation

RECIST evaluation68Ga-PET/CT evaluation

•functional volume •SUV•tumor/muscle SUV

Response to the treatmentFollow up: 6-15 months

RECIST Response SUV max Response

PR SD PD PR SD PD

Patients (11) 2 4 4 (1 NA) 2 4 5

Lesions

Lymph node (23) 18% 78% 4% 34% 52% 14%

Bone (130) NA NA NA 27% 33% 40%

Lung (20) 5% 90% 5% 39% 36% 25%

PR - partial responseSD - stable diseasePD - progression disease

According to EORTC criteria modified by ourEthics Committee

Before Before therapytherapy

Sept 2007

Mar 2009

After 4 cycles After 4 cycles

9090Y-DOTATOC Y-DOTATOC

(cumulative dose 268 mCi)

Severe dyspnea No dyspneaO2-therapy: 6-7 hours/day No O2-therapy

B.M. male, 75 year old

SUVmax changes (%)

-80

-70

-60

-50

-40

-30

-20

-10

0

10

20

0 1 2 3 4 5 6 7

Treatment steps

SU

Vm

ax c

han

ges (%

)

Lung

Bone

Lymph node

B.M. male, 75 year old

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

Pre-therapy Post-therapy

P.M. female, 61 year old

MAX SUV

0

5

10

15

20

25

30

35

0 1 2 3 4 5 6 7 8

cicli di curaTreatment steps

pain no pain no pain pain

P.M. female, 61 year old

MAX SUV(ref)

0

10

20

30

40

50

60

0 1 2 3 4 5 6 7 8

cicli di cura

Tumor/muscle SUV

Treatment steps

pain no pain no pain pain

P.M. female, 61 year old

Patient Tg pre-

treatmentTg post-

treatment68Ga-PET

SUVRECIST

1 >1000 stable PR PR

2 300 stable PD PD

3 0.5 stable PR PR

4 <0.3 stable SD SD

5 >6000 stable PD PD

6 380 increased PD PD

7 7500 stable SD SD

8 385 increased PD PD

9 0.4 increased SD SD

10 227 stable SD SD

11 200.000 increased PD PD

Tireoglobulin in comparison with treatment response

PR - partial response SD - stable disease PD - progression disease

Results

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

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

Side effectsImpact on renal function

Side effectsImpact on blood platelets

Side effectsImpact on WBC

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.

Grazie per l’attenzione

Ponte di CalatravaReggio Emilia