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PET/CT in thyroid cancer

Michael C. Kreissl
Dept. of Radiology and Nuclear Medicine,
Otto-von-Guericke University Magdeburg, Germany
michael.kreissl@med.ovgu.de
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Disclosure
Funding for Advisory Boards & Talks:
- AstraZeneca (Selumetinib, Vandetanib)
- SOBI (Cabozantinib)
- Bayer (Sorafenib)
- Eisai (Lenvatinib)
- SanofiGenzyme
- Ipsen (Cabozantinib)
- General Electric
No incentives or stocks
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PET/CT in thyroid cancer

• How it works
• What do the guidelines say?
• Methodological aspects
• Results and examples
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Tracers

• 18F-Fluorosedoxyglucose = „PET workhorse“

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FDG-PET

Glucose metabolism
no substrate for
FURTHER Phosphogluco-isomerase
GLYCOLYTIC
PATHWAY
no significant
OPO33-
dephosphorylation
and
18F no passive
diffusion
of charged
molecules

Hexokinase

FDG = [18F]-Fluorodesoxyglucose 18F

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FDG-PET
When?!
• Proven role in the localization of disease in Tg-positive, RAI scan–
negative patients (especially if Tg is > 10 ng/ml)
• Initial staging and FU of high-risk patients with PDTC or advanced
Hürthle cell carcinoma
• As powerful prognostic tool for identifying which patients
with distant metastases
• As selection tool to identify those patients unlikely to respond
to additional RAI.
• As a measurement of posttreatment response (EBRT, TKI, ...)

2015 ATA Guideline

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F-18-FDG-PET – practical aspects

Procedure (in Magdeburg): PET/CT

Standard protocol:
- ~ 250 MBq FDG, fasting, imaging about 60 min. p.i.
- In THW / after rhTSH / under LT4
- No speaking!
- Keep the patient warm (young pt: beta blocker)!
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F-18-FDG-PET – practical aspects

Important points:
• If before RAI: no oral / i.v. contrast agents!
• If after RAI: i.v. / oral contrast allowed
• Include CT-chest (full dose CT)
• Consider dedicated neck acquisition

© UKMD
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F-18-FDG-PET – practical aspects

(Preoperative) Staging:
Smith at al. 2008:
23 pt. foll. neoplasia by FNA
FDG-PET at various times post injection
-> 5 carcinomas (SUV 2.9 – 44.8)
-> 18 benign (SUV 0.9 – 38.2)

ATA 2015
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FDG-PET for follow-up of thyroid cancer:

Review of the literature

18 publications 1998 - 2004, 714 DTC patients.

In non RAI-avid disease (n = 789):
Sensitivity: 83%
Sensitivity: Median 85% (47 - 100%)
Specificity: 84%
Leboulleux et al. 2007
Specificity: Median 50% (25 - 100%)

Conclusion: FDG-PET is indicated in patients with positive TG (> 10

ng/ml) and negative I-131 WBS, TSH stimulation is not absolutely
necessary

Stokkel et al Quart J Nucl Med 2006

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[18F]FDG-PET
foll.-onc. DTC pT2bN0M0

On LT4-
Suppression
Tg: 0.7 ng/ml

After rhTSH
Tg: 3.7 ng/ml

Petrich et al.,
Nuklearmedizin 2001

KP 220948
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FDG-PET
“Real time prognosis for metastatic thyroid
cancer based on FDG-PET Scanning”

Robbins
JCEM 2006
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FDG-PET

The „Flip-Flop“-Phenomenon

Observation:

FDG-avid DTC lesions have low Iodine-uptake

(Iodine-avid DTC lesions have lower FDG-uptake)
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F-18-FDG-PET
PET-CT: Better than PET only?!

40 pts, 127 lesions

Sensitivity Specificity
FDG-PET 79% 76%
CT 79% 71%
Side by side 95% 76%
PET-CT 95% 91%

Palmedo et al J Nucl Med 2006

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I-124-PET
Background :
Same as I-131:
- Uptake into thyroid cells by Na-I-Symporter

I-124 is a PET tracer, T1/2= ~4 days

-> suitable for high resolution imaging
-> suitable for dosimetry (challenging!)
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I-124-PET
Procedure :
- In hypothyreosis or after rhTSH
- Injection of 50-100 MBq I-124

- Image acquisition 3-4 h and 24 h p.i (for dosimetry later time points)

When to do it: Could replace I-131-WBS

But: - limited availability
- more expensive than I-131
- no/low reimbursement
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I-124-PET
Indication: (Re-)Staging
- I-124 is superior to
I-131 (diagnostic) imaging!
- Small lung mets. may be negative

Example:
56 yo pt, FTC
Suppr. TG: 6420 ng/ml

FDG-PET prior to RAI

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I-124-PET
Indication: (Re-)Staging
- I-124 is superior to
I-131 (diagnostic) imaging!
- Small lung mets. may be negative

Example:
56 yo pt, FTC
Suppr. TG: 6420 ng/ml
I-124-PET prior to RAI (~50 MBq)
4 hours p.i. and after rhTSH
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I-124-PET
Indication: (Re-)Staging
- I-124 is superior to
I-131 (diagnostic) imaging!
- Small lung mets. may
be negative

Example:
56 yo pt, FTC
Suppr. TG: 6420 ng/ml
Posttherapeut. WBS after 21 GBq I-131
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Somatostatin receptor (SSR) imaging

Background:
• SSR occur in normal thyroid tissue
• SSR may be overexpressed in DTC / MTC (mainly SSR-2)
Agents:
• In-111-Octreotide (Scintigraphy)
• Ga-68-DOTA-TOC/-TATE/-NOC (PET)
• Labeled with Y-90, Lu-177 (Therapy)
= PRRT

SSR may be detected in 19-100%

of all DTC patients using In-111-octreotide
scintigraphy (Teunissen et al. 2006)
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Somatostatin receptor (SSR) imaging

Ga-68-DOTATOC-PET: Better sensitivity than SSR-Scintigraphy
Gabriel et al. 2007: In neuroendocrine tumors sensitivity 52%  97%, spec. 92%  92%

PET Scinti.

RVL LDR
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Somatostatin receptor (SSR) imaging

Ga-68-DOTATOC-PET: Own data in radioiodine negative / resistant FTC
SSR expression:
Low
(n=13)
None 23%
New foci: 2 patients 31%
Medium
Discordant foci 15%
as compared to FDG-PET: 3/4 patients Strong
31%

Versari et al., Thyroid 2014:

• Positive uptake in about 50% of RIA-negative patients
• One third showed strong uptake (suitable for PRRT)
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Somatostatin receptor (SSR) imaging

Example: 57 yo patient: osseus, pulmonal, pleural and lymph node

metastases,
after 53 GBq I-131,Tg: 49,425 ng/ml Ga-68-DOTATOC-PET
Bone Scan SUVmaxtumor:
13.5
SUVmeanliver: 6.5

Multiple new foci as compared to CT and bone scan CT;

radiopeptide therapy possible
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Somatostatin receptor (SSR) imaging

Example: 51 yo patient: osseus, pulmonal and lymph node metastases,

after 19.2 GBq I-131,Tg: 1957 ng/ml

FDG-PET Ga-68-DOTATOC
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Somatostatin receptor (SSR) imaging

Example: 51 yo patient: osseus, pulmonal and lymph node metastases,

after 19.2 GBq I-131,Tg: 1957 ng/ml

FDG

Ga-DOTA-TOC

FDG-PET Ga-68-DOTATOC
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Somatostatin receptor (SSR) imaging

Example: 51 yo patient: osseus, pulmonal and lymph node metastases,

after 19.2 GBq I-131,Tg: 1957 ng/ml CT

Ga-DOTA-TOC

FDG-PET Ga-68-DOTATOC
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Somatostatin receptor (SSR) imaging

84 yo patient: (new) pulmonal and lymph node metastases,

after 17 GBq I-131,Tg: 8660 ng/ml

Complementary information from all 3 studies

Strong „flip-flop“-phenomenon
Diagnost. whole body
scan after 300 MBq I- FDG-PET Ga-68-DOTATOC
131
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FDG-PET: monitoring therapy

49 yo female pat. with PDTC, initially pT4b N0 M1 pulm

12/13 3/14 5/14

TG (ng/ml): 240 TG: 690 TG: 2600
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FDG-PET: monitoring therapy

49 yo female pat. with PDTC, initially pT4b N0 M1 pulm

12/13 3/14 5/14 8/14

TG (ng/ml): 240 TG: 690 TG: 2600 TG: 120 Kreissl et al. Nuklearmedizin 2015
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FDG-PET: monitoring therapy

49 yo female pat. with PDTC, initially pT4b N0 M1 pulm

5/14 8/14 11/14

TG: 2600 TG: 120 TG: 260
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FDG-PET: monitoring therapy

49 jährige Pat. mit wenig diff. SD-Ca, initial pT4b N0 M1 pulm R1

5/14 8/14 11/14 02/15

TG: 2600 TG: 120 TG: 260 TG: 1200
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Beispiel
49 jährige Pat. mit wenig diff. SD-Ca, initial pT4b N0 M1 pulm R1

5/14 8/14 11/14 02/15 08/15

TG: 2600 TG: 120 TG: 260 TG: 1200 TG: 4000
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Conclusion
• For staging FDG is the tracer of choice in RAI refractory
and advanced disease (indicator of aggressiveness)
• Take guideline as guidance not rule (low Tg does not rule out
advanced disease especially in cases with unfavorable hist.)
• In complicated cases consider other imaging modalities,
such as SSR-imaging (but also others..)
• Restaging in RAI-refractory disease should be performed with
FDG
• I-124 may replace (in part) I-131-WBS
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Thanks für your attention!