Uso do PET no acompanhamento e na detecção de metástases do

Uso do PET no
acompanhamento e na
detecção de metástases
do Câncer de Tireóide
CBAEM
Aracajú,2005
POSITRON
EMISSION
TOMOGRAPHY
Decaímento de Positron
+ positron (e+ )
+
18F
18F
“18F
18O
18O
+ e+ + ν + Energy
decai por emissão de positrons”
Positron Annihilation
511 keV
+ -
e+
+
511 keV
γ
γ
SISTEMAS DE DETECÇÃO
PET
Hybrid PET/SPECT
Sensitivity
SPECT
(collimated detector)
Radioisótopos
FDG Principles :
Increased glucose metabolism as universal
sign of malignant disease
Glucose transporter proteins (GLUT-1)
Hexoquinase
Glucose 6-phosphatase
FDG
FDG 6-phosphatase
Rationale of PET with FDG
9 Glucose transporter in malignant cells up
-regulated
up-regulated
9 Phosphorylation ((hexokinase)
hexokinase) in malignant cells is
activated
9Decrease of FDGlucose
-6-phosphatase
FDGlucose-6-phosphatase
FDG in tumor cells
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.
Why use PET in the follow
up of Thyroid cancer ?
When is Pet Indicated in patients with
thyroid carcinoma ?
1) Measurable Thyroglobulin
serum
levels
without
detection of radioiodine
accumulating tissue ((after
after
complete
ablation
of
thyroid
thyroid)) = TG +, PCI Recurrences of DCT have often lost the ability to
concentrate radioiodine (RI), while increasead
glucose metabolism is present.
Possible reasons : mutation and/or selection of
iodine negative tumor cells due to RI-therapy
When is Pet Indicated in patients with
thyroid carcinoma ?
2)
9High risk patients
9TG – or very low
-tg
low,, anti
anti-tg
+
9PCI –
Recurrences of DCT have often lost the ability to
concentrate radioiodine (RI) and to produce TG.
PCI -, Tg + / PET +
PCI -
Rx Tórax +
PET +
77 a, Fem, Ca Pap
Meta pulmonar e óssea
2 doses de RAI
PCI –, Tg +
Rx Tórax +
PET + Metas Múltiplas
Wang, W. et al. J Clin Endocrinol Metab 1999;84:2291
- 2302
PCI – Tg + / PET +
- 68 a, fem, Ca pap
- RX Tórax +
- PCI – pós 250 mCi
- PET + Tumor paratraqueal
- Cirurgia – Ca Folicular
Wang, W. et al. J Clin Endocrinol Metab 1999;84:2291
- 2302
PCI -, Tg =1, anti-Tg + / PET +
PCI -
PET +
CT +
PCI
Pós dose - 50 a, masc, Ca Pap
- PCI – Pós ablação
- Tg = 1, anti-Tg +
- PET + Pulmão
-CT +
-300 mCi
-PCI Pós dose –
- Remoção cirúrgica
Wang, W. et al. J Clin Endocrinol Metab 1999;84:2291
- 2302
When is Pet Indicated in patients with
thyroid carcinoma ?
9When you want to find lesions that can be
surgically resected or stabilized ( Radiation or
embolized ) in residual or recurrent disease
disease..
- In high risk patients
- When markers are +
- When other imaging methods have failed
Coronal
Transaxial
Chin, B. B. et al. J Clin Endocrinol Metab 2004;89:91- 95
75 a, fem , Ca papilífero,
Tg +, PCI - , dor torácica
PET +, RM +
Cirurgia
PET
PCI
Coronal
RM
Sagital
Sagital
49 a, masc, pT2bN0M0
PCI neg, Tg +, PET +
Cirurgia
PET -
57 a, fem, pT4bN1Mx,
2 PCI –
PET +
Cirurgia
PET +
Radioterapia
PET +
PCI
PET
Accuracy of FDG PET in Thyroid
Carcinomas
9 ~ 70%
9Dependent of the degree of dedifferentiation
(The more ““malignant”,
malignant”, the more FDG uptake
uptake))
PET / Falso Positivo
- 77 a, masc, Ca papilífero
- Tg +, PCI – pós ablação
- 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;84:2291
- 2302
PET / Falso Positivo
CT +
PCI +
- 54 a, Fem , Ca pap
-Tiroidect sem ablação
- CT + em Pulmão
- PCI + em Leito tiroideano
- Ablação
- PCI - Pós ablação
- PET +
- Biópsia = Granuloma
PCI -
PET +
Wang, W. et al. J Clin Endocrinol Metab 1999;84:2291
- 2302
PET / Falso Negativo
PCI -
PET -
PCI pós dose
-42 a, Fem, Ca Pap
-TG + pós ablação
- PCI e PET negativos
- 230 mCi
- PCI +
Wang, W. et al. J Clin Endocrinol Metab 1999;84:2291
- 2302
PET / Falso Negativo
PCI -
PET -
- 45 a, Fem , Ca pap
- Tg +, anti-tg +
- PCI e PET - US cervical +
- PCI + Pós 200 mCi
Wang, W. et al. J Clin Endocrinol Metab 1999;84:2291
- 2302
Better Pet accuracy with high TSH ?
Relationship between TSH and FDG
Uptake by Thyroid Cells
9 TSH activates ((indirectly)
indirectly) glucose transport
Sisson et al, JCEM 1993
9 Thus
Thus,, higher accumulation of FDG in thyroid cancer
cells could be expected in case of an elevated serum
TSH.
FDG PET in DTC under Endogenous TSH
(PET under suppression x PET Hypothyroisis)
Moog et al (J Nucl Med 2000 Dec; 41(12):1989
-95)
41(12):1989-95
Elderly patients with known metastatic disease
N=10 (7 fol
), 17 lesions
fol,, 3 pap
pap),
PET in euthyrosis (TSH
↓) vs
↑):
(TSH↓)
vs.. PET in hypothyrosis (TSH
(TSH↑):
Increase of 63, 1% uptake in tumor lesions (TBR)
Van Tol et al (Thyroid
-7 )
Thyroid,, 2002 May
May;; 12(5):381
12(5):381-7
Younger patients with suspicious recurrence
N=8 (2 fol
fol,, 6 pap
pap))
Better results (5/8) under endogenous TSH
-simulation
TSH-simulation
compared to supression
Hypothesis
→
Exogenous TSH stimulation (rh TSH)
plus hormone medication might cause maximal
activation of FDG uptake by thyroid carcinoma cells (?)
Hannover Study
Patients
Patients::
Ages:
Histology
Histology::
TNM/Stage
n=30 (19w, 11m) DTC
55 + 13 years
21 pap
pap,, 9 fol
pT1a N0 M0 – pT4b pN1b pM1 / II-IV
-IV
9 Suspicion of tumor because of:
– Thyroglobulin
Thyroglobulin levels
levels:: increased
increased borderline
borderline
– MIBI
-Scan, radioiodine
MIBI-Scan,
radioiodine scan
scan,, morphology
morphology negative
negative or equivocal
--Serum
Serum glucose level
Exclusion of
level:: normal ((Exclusion
of diabetes
diabetes patients
patients))
Petrich T, Eur J Nucl Med Mol ,2002
FDG-PET in euthyrosis with and without
recombinant TSH – Timetable
Continuing T4 - medication
0.9 mg
Thyrogen
PET (1)
400 MBq
FDG I.v.
PET (2)
400 MBq FDG I.v.
+
400 MBq
131
I131
Scan (72h
(optional)
0.9 mg
Thyrogen
Scan (48h)
1-2 meses
0
Tg/TSH
day
1
Tg/TSH
2
3
Tg/TSH
4
5
Tg/TSH
6
Results
Under suppression:
PET + 9/30
After rh TSH :
PET + 19/30
Impact on therapy
Follow
-up FDG
-PET with rh TSH
Follow-up
FDG-PET
9 After tumor detection
detection::
Change of therapy
therapy::
No change
Without tumor detection
detection::
17/19 Pat
7 OP
2 RIT
3 RIT/rediff
5 Rediff
2
0
Citation
Pts
Change in SUV
when TSH high
notes
Sisson et al
JCEM 77: 1090,1993
1
Increased
Hypothyroid
Wang et al
JCEM 84: 2291,1999
4
12 % increase
rhTSH
Moog et al
JNuc Med 41: 1989,2000
10
63 % increase
Hypothyroid
Van Tol et al
Thyroid 12:381,2002
8
Increased
Hypothyroid
Petrich et al
EjNM 29:641,2002
30
35 % increase
rhTSH
Chin et al
JCEM 89:91,2004
7
72 % increase
rhTSH
Well and less differentiated cancer cells
may be present in the same patient
PCI
PET
Combination of WBS + PET + rh TSH
Well and less differentiated cancer cells may be
present in the same patient
Combination of WBS and PET after hormone withdrawl or after
intramuscular 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, 17-21
Better Pet accuracy
machines
with better
?
PET-CT
I124-Iodide PET / CT in Thyroid Cancer
Registered / Fused Transverse Images
Courtesy of Dr. Steven M Larson, MSKCC
PET for Prognosis
FDG-PET scan can identify high risk subsets in patients
with metastasis : Prognostic Value
-125 patients - 41 month of follow up
-TG and WBS
-PET
Of PET + Patients
High rates of uptake
High volume of FDG-avid
Disease ( > 125 ml)
< years survival probability
Wang W, JCEM 2000, 1107-13
Pet uptake x Survival
1.00
FDG -
0.75
3/179 deaths
0.50
(p <0.001)
Median survival = 53 mo
0.25
FDG +
93/221 deaths
0.00
0
10
20
30
40
Months
50
60
70
80
90
SUV x Survival
1.00
SUV = 0
0.75
SUV= 0 - 4.6
0.50
SUV= 4.74.7-7.2
SUV= 7.37.3-13.3
0.25
SUV> 13.3
0.00
0
10
20
30
40
50
Months
60
70
80
90
PET and Thyroid Incidentalomas
PET INCIDENTALOMAS
8 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 1517-20, 2002
Conclusions
-FDG-PET uptake in residual/recurrent thyroid CA
is a marker of biologic tumor behavior which
correlates with tumor aggressiveness.
-FDG uptake appears to be a better marker of
tumor aggressiveness than Tg which ca be low in
tumors which have undergone dedifferentiation.
Conclusions
-It may be helpful in some patients by showing
site of cancer which had not been identified by
other imaging tests
-Pet is not infallible in this group of patients: both
false positive and false negative may occur.
-PET scan is not required and not recommended
for routine follow up.
Conclusions
9 For DTC tumor imaging FDG
-PET appears to be useful
FDG-PET
in hypothyroidism ((or
or after administration of rh TSH
in euthyrodism
euthyrodism)) in combination with WBS.
- Injection of Thyrogen (0.9mg I.M.) on day 1 + 2 prior to
FDG
-PET
FDG-PET
- Fasting for 12 hours prior to PET
- If necessary
, normalization of serum glucose levels
.
necessary,
levels.