Download Nuclear Medicine Imaging of Thyroid Cancer Nuclear Medicine

5/8/2015
Nuclear Medicine Imaging
of Thyroid Cancer
Jolanta M. Durski, MD
Mayo Clinic Rochester MN
DISCLOSURE
Relevant Financial Relationship(s)
None
Off Label Usage
PET tracers which are not FDA approved yet
1
5/8/2015
I will talk about:
• Whole body radioiodine scan for DTC:
• When to do it: prior to ablation, post therapy, follow up
• How to do it:
•
Radiopharmaceuticals: I-131 versus I-123 (physical properties, cost,
•
•
Imaging: whole body, image acquisition, processing, SPECT/CT,
Patient preparation (including rhTSH use)
stunning, dose etc.)
• PET/CT for thyroid cancer
•
18F-FDG
•
•
•
PET/CT
Principles, patient preparation (? rhTSH), cost & reimbursement
Use for Differentiated Thyroid Cancer, Anaplastic, Hurthle cell,
Medullary & Thyroid Lymphoma
Incidental thyroid uptake on FDG-PET
• Other non FDA approved PET tracers
•
•
•
I-124 PET/CT
F18-Fdopa,
Ga68-octreotide
Whole Body Radioiodine Scans
at Mayo Clinic in Rochester MN
ÿ 150 diagnostic whole body scans per year ÿ 50 post-treatment scans
Decreasing trend reflects a change in guidelines –
no remnant ablation in low risk patients
2
5/8/2015
Radioiodine Scan for
Differentiated Thyroid Cancer
When to do it?
When to do radioiodine scan
Radioiodine Scan
Prior to Remnant Ablation
To do or not to do?
That is the question
3
5/8/2015
When to do radioiodine scan
Radioiodine Scan
Prior to Remnant Ablation
SNMMI:
YES!
ATA: if expected to change management!
•
•
•
•
No remnant – no need for remnant ablation
Large remnant – risk of radiation thyroiditis - surgery or smaller dose
Neck nodal metastases – surgery, alcohol ablation, increased dose
Distant metastases – larger dose, dosimetry, steroids for CNS met,
possibly local treatments
• Occasional unexpected uptake e.g. breasts – postpone therapy
The utility of radioiodine scans prior to iodine 131 ablation in patients with well-differentiated thyroid cancer.
Van Nostrand D, Aiken M, Atkins F, Moreau S, Garcia C, Acio E, Burman K, Wartofsky L.Thyroid. 2009 .
355 sets of scans 55% of patients had findings that might have altered the management prior to ablation.
When to do radioiodine scan
Radioiodine Scan
Prior to Remnant Ablation
• 34 y/o man with papillary thyroid
cancer metastatic to neck nodes,
underwent thyroidectomy and
bilateral neck dissection
• Additional bilateral neck nodes seen
on the pre-ablation scan
• Additional surgery & 131I dose
increased to 200 mCi
4
5/8/2015
When to do radioiodine scan
Radioiodine Scan
Prior to Remnant Ablation
• 28 year old woman with
papillary thyroid cancer,
post near-total
thyroidectomy
• Radioiodine uptake 0.1 %
• Radioiodine remnant
ablation was cancelled after
scan
When to do radioiodine scan
Post-therapy 131I Scan
recommended by ATA
More lesions than diagnostic I-131/I-123 scan
13% of scans, 9% change in management*
*Are posttherapy radioiodine scans informative and do they
influence subsequent therapy of patients with differentiated
thyroid cancer? Fatourechi V, Hay ID, Mullan BP, Wiseman GA,
Eghbali-Fatourechi GZ, Thorson LM, Gorman CA. Thyroid. 2000
(117 patients)
usually not enough uptake for I-131 treatment**
Clinical outcomes following empiric radioiodine therapy in
patients with structurally identifiable metastatic follicular cellderived thyroid carcinoma with negative diagnostic but positive
post-therapy 131I whole-body scans. Sabra MM, Grewal RK,
Tala H, Larson SM, Tuttle
RM.
2 to 10 days after treatment (ATA guideline)
• Tumor to background increases with time (clearance from other tissues)
• Variable effective half life in cancer tissue (0.7 to 7days***)
**Determining the appropriate time of execution of an I-131 post-therapy whole-body scan: comparison between early and late imaging. Salvatori M, Nucl Med Commun. 2013
(134 patients) 3d scan more info in 7.5% of patients 7d scan more info 12% of patients***
5
5/8/2015
When to do radioiodine scan
Follow up Diagnostic Whole
Body Radioiodine Scan
(after remnant ablation)
When evidence of recurrent disease: elevated
Thyroglobulin, anti-Tg antibody, evidence of mets on other imaging or
post ablation scan, high risk of persistent disease etc….
Not indicated: low risk or intermediate risk patients with
undetectable Tg on replacement, negative anti Tg ab and negative US
(ATA guidelines)
……..more details later in this session……
radioiodine scan examples
Whole Body Radioiodine Scan
Papillary thyroid cancer metastases
26 y/o woman with papillary thyroid cancer 8 yrs after thyroidectomy
Multiple surgeries for nodal disease. Rising thyroglobulin (14) Tx 100 mCi
123I
anterior
Diagnostic scan
posterior
4 days post therapy scan
anterior
posterior
Additional lesions in the neck and lungs on the post treatment scan
6
5/8/2015
radioiodine scan examples
Whole Body Radioiodine Scan
Papillary thyroid cancer metastases
29 y/o man presented with stridor, slowly growing large thyroid mass.
Thyroidectomy, bilateral lateral neck dissection August 2011. 305 mCi I-131(with rhTSH) Sept 2011
Liver uptake
Physiologic on
post tx scan
123I
Diagnostic scan Sept 2011
Thyroglobulin 78
5 days post therapy
Diffuse lung uptake
Tiny (up to 3 mm) nodules on CT
Follow up scan June 2013
Thyroglobulin 2.6
radioiodine scan examples
WB 123I scan - Skeletal Metastases
follicular thyroid cancer
• 56 y/o woman presented in 2012 with skeletal mets from follicular thyroid cancer.
• History of lobectomy for goiter. Completion of thyroidectomy Aug 2012. No malignancy ever
found in thyroid.
• Treatment with 300 mCi with Thyrogen Oct 2012
• External radiation to left humerus and T12
Diagnostic 123I scan :
Follow up 123I scan :
April 2014 doing well
no evidence of recurrence
Tg 0.6 no ab
Oct 2012
Thyroglobulin 894
March 2013
Thyroglobulin 0.6
7
5/8/2015
Radioiodine Scan for
Differentiated Thyroid Cancer
How to do it?
How to do radioiodine scan
Iodine 123 versus Iodine 131
Only 20% of I-131 gamma rays are stopped by standard
gamma camera crystal versus 100% for I-123
I-123 γ energy 159 keV
(good)
I-131 γ energy 364 keV
(too high)
8
5/8/2015
How to do radioiodine scan
Iodine 123 versus Iodine 131
I-131 3% - 5% septal penetration (high energy collimator)
only 0.1 – 0.3 % for I-123
This effect is most visible
when there is a point source,
much hotter than other areas in the field of view
I-123 γ energy 159 keV
(good)
I-131 γ energy 364 keV
(too high)
How to do radioiodine scan
Iodine 123 versus Iodine 131
Superiority of iodine-123 compared with iodine-131 scanning for thyroid remnants in
patients with differentiated thyroid cancer. Mandel SJ, et al Clin Nucl Med. 2001
9
5/8/2015
How to do radioiodine scan
Iodine 123 versus Iodine 131
No β radiation
β radiation
Half life 13 hours
Half life 8 days
Lower dose to the patient
Higher dose to the patient However,
longer half life allows for dosimetry
Cost $306 per 2 mCi
Cost $114 per 2 mCi
(including $100 delivery)
(including $100 delivery)
Stunning is more likely
How to do radioiodine scan
Stunning ?
Diagnostic dose of 131I prevents accumulation of the therapeutic dose
Diagnostic scan
Post therapy
Lower dose of 131I (2 mCi)
Demonstrated in a study of cultured thyroid cells*
Stunning of iodide transport by (131)I irradiation in cultured thyroid epithelial cells.
Postgård P et al. J Nucl Med. 2002
Reduced iodide transport (stunning) and DNA synthesis in thyrocytes exposed to low absorbed doses from 131I in vitro.
Lundh C et al. J Nucl Med. 2007
Iodine transport was reduced at 0.15 Gray (50% reduction at a 3 Gray dose)
equivalent to doses after diagnostic scans.
DNA measurement showed reduction in cell numbers at 8 Gy
10
5/8/2015
How to do radioiodine scan
Is There Stunning After
123I
?
Yes, but less than with 131I
* Radiation-induced thyroid stunning: differential effects of (123)I, (131)I, (99m)Tc, and (211)At on iodide transport and
NIS mRNA expression in cultured thyroid cells. Lundh C, et al. J Nucl Med. 2009
stunning effect per unit of absorbed dose is more severe
with 123I than 131I * (about 2x) (internal conversion followed by Auger electrons)
However, the absorbed dose is about 100 x higher with 131I**
(the difference may be smaller for small metastatic lesions)
** Biokinetics of iodide in man: refinement of current ICRP dosimetry models.
Johansson L et al. Cancer Biother Radiopharm. 2003
How to do radioiodine scan
Radioiodine Scan
Dose and Image Acquisition
Iodine-123
1.5 – 3 mCi (ATA guideline)
Iodine 131
1 – 3 mCi (ATA guideline)
SNMMI up to 5 mCi (Mayo 5mCi)
Whole body image at 24h
Whole body image at 48h
Medium energy collimator
High energy collimator
11
5/8/2015
How to do radioiodine scan
Radioiodine Scan
Image Processing
• Uptake in the
neck
• Uptake in the
metastatic
lesions
• Whole body
retention
How to do radioiodine scan
SPECT/CT
more accurate than planar imaging
• remnant thyroid tissue versus nodes
• physiological uptake versus metastases
At Mayo routine neck & upper thorax,
additional areas as needed
• Salivary, GI, Lacrimal uptake
• Contamination artifacts
• detects more metastatic lesions
• better localization of metastases
• fewer additional tests & mistakes
Value of ¹³¹I SPECT/CT for the evaluation of differentiated thyroid cancer: a
Xue YL, Qiu ZL, Song HJ, Luo QY. Eur J Nucl Med Mol Imaging. 2013
systematic review of the literature.
1066 patients
Incremental diagnostic value over planar imaging in 48% to 88% of patients
Modification of therapeutic strategies in 25% of patients
12
5/8/2015
SPECT/CT
SPECT/CT Physiologic 123I Uptake
in the Esophagus
SPECT/CT
SPECT/CT Lingual Remnant and
Tissue in the Thyroglossal Tract
13
5/8/2015
SPECT/CT
123I
SPECT/CT Thyroid Remnant
SPECT/CT
123I
SPECT/CT
Residual Thyroid Tissue and Lymph Node Metastasis
Uptake in the neck 3.3%
14
5/8/2015
SPECT/CT
123I
SPECT/CT
Recurrent Differentiated Thyroid Cancer
Normal uptake in hiatal hernia
SPECT/CT
Radioiodine Avid Mediastinal
Metastases 123I SPECT/CT
Thyroglobulin 332 decreased to 22 after 150 mci
15
5/8/2015
SPECT/CT
Radioiodine Avid Pulmonary
Metastases 123I SPECT/CT
SPECT/CT
123I
SPECT/CT Skull Metastasis
salivary pooling
After 131-I Tx
16
5/8/2015
How to do radioiodine scan
Radioiodine Scan
Patient Preparation
• Low Iodine diet
• wait 6-8 weeks post iodinated iv contrast
• Pt not lactating (stop for 6 weeks, diagnostic scan helpful),
• not pregnant
• Thyroid hormone withdrawal (TSH goal 30)
• RhTSH
How to do radioiodine scan
rhTSH Prior to Radioiodine Scan
Mayo Clinic Rochester
Thyroid Hormone Withdrawal
Patients can avoid
symptoms of hypothyroidism
Thyrogen
Faster renal clearance!
decreased dose to the patient
with subsequent remnant ablation
Cost: $1,381 per box (2 vials)
• Most useful for
• Patients that can not tolerate withdrawal
• Patients unable increase endogenous TSH:
• Large remnant
• Pituitary insufficiency
17
5/8/2015
How to do radioiodine scan
rhTSH Scan Protocol
Mayo Rochester protocol
for rhTSH stimulated
scan & remnant ablation
Protocol:
rhTSH IM day 1 & 2
Day 1
scan dose day 3
rhTSH
Day 2
rhTSH
Day 3
Day 4
123I
5 mCi
scan
rhTSH
131I
Therapy
The effects last longer than the blood concentration levels
How to do radioiodine scan
Is radioiodine scan more sensitive
with THW versus rhTSH ?
*Comparison of administration of recombinant human thyrotropin with withdrawal of thyroid hormone for
radioactive iodine scanning in patients with thyroid carcinoma. Ladenson PW et al N
Engl J Med. 1997
** Recombinant human thyroid-stimulating hormone versus thyroid hormone withdrawal in the identification of
metastasis in differentiated thyroid cancer with 131I planar whole-body imaging and 124I PET.
Van Nostrand D et al J Nucl Med. 2012
***Preparation by recombinant human thyrotropin or thyroid hormone withdrawal are comparable for the
detection of residual differentiated thyroid carcinoma. Robbins RJ, Tuttle RM, Sharaf RN, Larson SM,
Robbins HK, Ghossein RA, Smith A, Drucker WD.J Clin Endocrinol Metab. 2001
Prospective study, 127 pts
Withdrawal more sensitive*
Significantly more foci of metastases of DTC
may be identified in patients prepared with
THW than in patients prepared with rhTSH.**
No difference in diagnostic accuracy***
Probably reduced uptake due to faster blood clearance with RhTSH,
(dose to the patient lower too),
this could be compensated by using I-123
****Iodine biokinetics and dosimetry in radioiodine therapy of thyroid
cancer: procedures and results of a prospective international
controlled study of ablation after rhTSH or hormone withdrawal.
Hänscheid H et al J Nucl Med. 2006
effective half-life in the thyroid tissue
significantly longer after rhTSH than during hypothyroidism****
18
5/8/2015
Selumetinib-enhanced radioiodine
uptake in advanced thyroid cancer.
…….more details later in this session……
Selumetinib-enhanced radioiodine uptake in advanced thyroid cancer. Ho AL, Grewal RK, Leboeuf R,
Sherman EJ, Pfister DG, Deandreis D, Pentlow KS, Zanzonico PB, Haque S, Gavane S, Ghossein RA,
Ricarte-Filho JC, Domínguez JM, Shen R, Tuttle RM, Larson SM, Fagin JA. N Engl J Med. 2013
PET/CT for Thyroid
Cancer
Imaging of locally recurrent and metastatic thyroid cancer with positron emission tomography.
Conti PS, Durski JM, Bacqai F, Grafton ST, Singer PA. Thyroid. 1999
19
5/8/2015
PET/CT
Principles of PET/CT
-
+
Positron is Beta (+) particle, Annihilates with electron
Two gamma rays 511 keV in opposite directions
Better resolution 4-5 mm (SPECT 8-10 mm)
Positron emitters are often isotopes of elements naturally present in the body (C,N,F,O)
39
PET/CT
F-18 Fluorodeoxyglucose
18F - FDG
Accumulates in malignant cells
• Increased metabolism & Warburg effect
Otto Warburg found in 1924 that cancer cells tend to
“ferment” glucose into lactate even in the presence of
sufficient oxygen to support mitochondrial oxidative
phosphorylation.
Malignant cells typically have glycolytic rates up to 200
times higher than those of their normal tissues of origin
F18-FDG
- 2-Deoxy-2-fluoro-D-glucose
• FDG is Phosphorylated in the cells, but not metabolized further
• Not re-absorbed in kidneys (good for imaging)
• Accumulates in inflammation
40
20
5/8/2015
PET/CT
FDG Normal Distribution
Brain - intense uptake
Thyroid – low uptake
Heart - variable uptake
Urinary tract - intense uptake
Liver SUV 3
Mediastinal blood pool 2.5
SUV
=
standard uptake value
radioactivity concentration in a selected part of the body
radioactivity concentration in the hypothetical case of
an even distribution throughout the whole body
PET/CT
18F-FDG
PET/CT
Patient Preparation
Fasting for 4 - 6 hours
No insulin for 4 hours
Insulin will cause diffuse muscle uptake
Glucose level < 200 mg/dl
Glucose competes with labelled glucose
Good hydration
to help clear the tracer from the background
No vigorous exercise for 24 hours
to avoid muscular uptake
21
5/8/2015
PET/CT
18F-FDG
PET/CT for
Differentiated Thyroid Cancer
Evaluation for residual or recurrent disease in patients with
Elevated Thyroglobulin & negative radioiodine scan
Less differentiated cancer =
glucose metabolism
17 studies 571 patients DTC & negative radioiodine scan*
Patient based sensitivity 84% specificity 84%
Lesion based sensitivity 92% specificity 78%
Best when stimulated TG >10 ng/ml**
ATA
recommended cut off
iodine uptake
*Value of 18F-FDG-PET/PET-CT in differentiated
thyroid carcinoma with radioiodine-negative
whole-body scan: a meta-analysis.
Dong MJ et al. Nucl Med Commun. 2009
**Role of ¹⁸F-fluorodeoxyglucose positron emission
tomography/computed tomography in patients affected by
differentiated thyroid carcinoma, high thyroglobulin level, and
negative ¹³¹I scan: review of the literature. Bertagna
F et al. Jpn J Radiol. 2010.
PET/CT
Papillary Thyroid Cancer
Iodine Negative 18F-FDG PET/CT Positive
Bone scan
123I
scan
18F-FDG
PET
22
5/8/2015
PET/CT
Metastatic Papillary Thyroid Cancer
F18-FDG PET/CT
Radioiodine scan
PET/CT
F18-FDG PET/CT
Same patient imaged 3 days apart:
FDG PET/CT
High FDG uptake in a
metastatic jugular chain
LN right side.
131I
salivary radioiodine
excretion
post-therapy SPECT/CT
No 131I uptake in the LN
Slide from Trond Velde Bogsrud, MD, PhD
Oslo University Hospital, Oslo, Norway, &
Aarhus University Hospital, Aarhus, Denmark
23
5/8/2015
PET/CT
High uptake of both 131I
and FDG in a metastatic
LN right lower neck
Slide from Dr. Trond Velde Bogsrud
High uptake of
both 131I and FDG
in metastasis in
the left kidney
PET/CT
18F-FDG
PET/CT for DTC
High jugular chain LNs metastases are not well seen on US
Case from Dr. Trond Velde Bogsrud
24
5/8/2015
PET/CT
18F-FDG
PET/CT for Thyroid Cancer
May be used regardless of Radioiodine scan result
Prognostic information*
*Real-time prognosis for metastatic thyroid carcinoma based on 2-[18F]fluoro-2-deoxy-D-glucose-positron emission tomography scanning.
Robbins RJ, Wan Q, Grewal RK, Reibke R, Gonen M, Strauss HW, Tuttle RM, Drucker W, Larson SM. J Clin Endocrinol Metab. 2006
(400 patients with thyroid cancer of follicular origin followed for median of 7.9 years,
221 positive metastases on initial PET)
• FDG positive metastases = much higher mortality (7x)*
• aggressiveness of therapy should match the FDG-PET status*
Used at Mayo to guide therapy choice for recurrent neck disease
• (surgery vs alcohol ablation vs radiation vs observation)
• especially for aggressive histology & after multiple surgeries
PET/CT
18F-FDG
PET/CT for DTC
Initial staging of high risk patients
Post-thyroidectomy assesment of DTC
with agressive histology*
*Postoperative fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography: an important imaging modality in patients
with aggressive histology of differentiated thyroid cancer. Nascimento C, Borget I, Al Ghuzlan A, Deandreis D, Hartl D, Lumbroso J,
Berdelou A, Lepoutre-Lussey C, Mirghani H, Baudin E, Schlumberger M, Leboulleux S.Thyroid. 2015 Apr
(38 consecutive patients with aggresive histology of DTC,
FDG PET/CT within 3 months of post-ablation scan)
• Metastases found in 53% of patients
• PET/CT more sensitive than post tx radioiodine scan*
• suggested routine use in patients with aggressive histology*
25
5/8/2015
PET/CT
Medicare Reimbursement of
18F-FDG-PET-CT for Thyroid
Cancer 2013 Change
1 PET/CT initial staging
plus
3 subsequent scans
Current pricing:
Whole body PET/CT
Nominal: $6,536.83
Medicare: $1,565.44
FDG
Nominal: $241.00
Medicare: $96
http://www.cancerpetregistry.org/pdf/
FinalNOPR-PET-Webinar-6-19-2013.pdf
PET/CT
18F-FDG
PET/CT for DTC
Role of Recombinant TSH
rhTSH used in PET 44% of time (TG positive radioiodine negative patients)
Survey of 288 ATA members
• Detects more lesions (Odds Ratio 4.9)*
• Detects more patients with true positive lesions (OR 2.5)*
• Better target to background*
• Change of management 9%*
• More sensitive for lesion detection (95 vs 81%)
• More sensitive for detection of involved organs (94 vs 79%)
• Not significantly different detection of patients (with any lesions)
7 prospective trials 168 patients
*The role of TSH for 18F-FDG-PET in the diagnosis of
recurrence and metastases of differentiated thyroid
carcinoma with elevated thyroglobulin and negative scan: a
meta-analysis. Ma C et al.Eur J Endocrinol. 2010
** Assessment of the incremental value of recombinant
thyrotropin stimulation before 2-[18F]-Fluoro-2-deoxy-Dglucose positron emission tomography/computed
tomography imaging to localize residual differentiated thyroid
cancer. Leboulleux S et al. J Clin Endocrinol Metab. 2009
largest trial 63 patients
Most useful when:
normal neck & chest CT scan & normal neck US & elevated, but not vey high TG
Reimbursement (negative radioiodine scan has to be documented)
Forms at Genzyme website: http://www.thyrogen.com/patients/TreatingwithThyrogen/ThyrogenCoverage/ThyrogenONE.aspx
26
5/8/2015
PET/CT
18F-FDG
PET/CT for Thyroid
Cancer
Mayo Clinic in 2013
PET/CT
PET/CT F18-FDG
Anaplastic Thyroid Cancer
• Very sensitive
• Useful for
• Evaluation for metastases (especially skeletal)
• Surgical planning
• Radiation therapy planning
• Evaluation of treatment response
• Changed management in 50% *
*18F-FDG PET in the management of patients with anaplastic
thyroid carcinoma. Bogsrud TV, Karantanis D, Nathan MA, Mullan
BP, Wiseman GA, Kasperbauer JL, Reading CC, Hay ID, Lowe VJ.
Thyroid. 2008
27
5/8/2015
PET/CT
PET/CT F18-FDG
Anaplastic Thyroid Cancer
PET/CT
18F-FDG
PET/CT
Hurthle Cell Carcinoma
• Intense FDG uptake
• Poor radioiodine accumulation
• 18F-FDG PET/CT very accurate
(sens. 96% spec.95%)*
*Diagnostic accuracy and prognostic value of 18F-FDG PET in Hürthle cell thyroid cancer patients.
Pryma DA, Schöder H, Gönen M, Robbins RJ, Larson SM, Yeung HW. J Nucl Med. 2006
28
5/8/2015
PET/CT
18F-FDG
PET/CT
Hurthle Cell Carcinoma
history of Hürthle cell cancer
complaint of diffuse aches.
CT indeterminate lung nodule with
some mediastinal adenopathy, US
and 131I scans negative. PET
image showed widespread bone
and lung metastases,
confirmed with right hilar biopsy.
18F-FDG PET of patients with Hürthle cell carcinoma.
Lowe VJ, Mullan BP, Hay ID, McIver B, Kasperbauer JL.
J Nucl Med. 2003
PET/CT
18F-FDG
PET/CT for
Medullary Thyroid Cancer
Suspected residual or recurrent MTC
Useful if calcitonin ≥ 1,000 ng/L
Pooled detection rate 75 % *
*Detection rate of recurrent medullary thyroid carcinoma
using fluorine-18 fluorodeoxyglucose positron emission
tomography: a meta-analysis. Treglia G, et al.
Endocrine. 2012
Low sensitivity if calcitonin < 1,000
FDG positive disease has worse prognosis**
Liver Metastasis
**The prognostic value of 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography in patients with suspected residual or
recurrent medullary thyroid carcinoma. Bogsrud TV, Karantanis D, Nathan MA, Mullan BP, Wiseman GA, Kasperbauer JL,
Reading CC, Björo T, Hay ID, Lowe VJ. Mol Imaging Biol. 2010
Sensitivity better for sporadic or familial MTC,
Worse for MEN2A***
*** Role of [(18)F]FDG-PET/CT in the detection of occult recurrent medullary thyroid cancer. Skoura E, et al.
Nucl Med Commun. 2010
29
5/8/2015
PET/CT
18F-FDG
PET/CT
Medullary Thyroid Cancer
Skeletal Metastases Calcitonin level 9691 pg/ml
PET/CT
F18-FDG PET/CT
Lymphoma Involving Thyroid
• 66 y/o man came to Mayo in Aug 2013 with 12-18 month hx. of enlarging goiter. Bx
Oct 2012 chronic thyroiditis.
• FNA 8/22/13 Hashimoto thyroiditis. Core needle biopsy: T cell lymphoma (very rare
pathology)
• FDG PET/CT 8/23/13. Suspicious for lymphoma or anaplastic thyroid cancer with nodal
involvement.
FDG-PET/CT is routinely used for
initial staging of lymphomas
and evaluation of response to therapy
30
5/8/2015
PET/CT
Incidental Thyroid Uptake
of F18-FDG (about 4% of PET/CT scans)
• Diffuse
• Incidence 0.1% - 4.5%, mean 1.9%
• usually represents Hashimoto thyroiditis ~ 85%*, occasionally
Graves’ disease*, 4% malignancy**
• Focal
• Incidence 0.1% - 4.8%, mean 2.0% in Asia
• 10%- 65%, mean 36% malignant ** (24% to 74%)
• Higher SUV in malignant (large overlap)
• Benign SUV 4.8 (3.1 SD)
• Malignant SUV 6.9 (4.7 SD)
*Clinical significance of diffusely increased 18F-FDG uptake in the thyroid gland. Karantanis D, Bogsrud TV,
Wiseman GA, Mullan BP, Subramaniam RM, Nathan MA, Peller PJ, Bahn RS,
Lowe VJ. J Nucl Med. 2007
**Risk of malignancy in thyroid incidentalomas detected by 18F-fluorodeoxyglucose
positron emission tomography: a systematic review. Soelberg KK, Bonnema SJ, Brix TH, Hegedüs L.
Thyroid. 2012 (125,000 subjects)
PET/CT
Incidental Thyroid Nodule (ITN)
ACR Recommendation
ITN on CT, MRI or ultrasound (no suspicious imaging features, normal life expectancy)
• - further evaluation with dedicated thyroid ultrasound only if:
• Nodule ≥1 cm in a patient age <35 yrs.
• Nodule ≥1.5 cm in a patient age ≥35 yrs.
Focal metabolic activity in the thyroid on
18FDG-PET
- both dedicated thyroid ultrasound
and FNA of the PET-avid lesion (if normal life expectancy)
Focal activity in the thyroid on other nuclear med. studies - ultrasound
Managing Incidental Thyroid Nodules Detected on Imaging: White Paper of the ACR Incidental Thyroid Findings Committee Hoang
JK et al. J Am Coll Radiol. Nov. 2014
31
5/8/2015
PET/CT
Incidental Thyroid F18-FDG Uptake
2014 ATA guideline:
Diffuse uptake
÷
TSH & US to ensure that
there s no clinically evident nodularity”
Focal uptake
÷ TSH
• Low TSH
radioiodine thyroid scan & uptake
• Normal or high TSH
US, clinical evaluation
and FNA
PET/CT
Future PET/CT
Radiopharmaceuticals
Available in Europe and as a research tool in some US institutions
Not FDA approved for routine use
Require IND application to FDA
32
5/8/2015
PET/CT
Iodine-124
131I
124I
Positron Emitting Radioiodine
Van Nostrand D
• Better resolution of PET vs SPECT
• 2 X PET 4-5 mm SPECT 8-10 mm
Thyroid. 2010; 20: 879-83.
• Not as good as F-18 High energy of positrons 2.1 MeV (23% abundance) mean range in tissue about 3.5 mm
(compared to 0.6 mm for F18) High energy gamma photon (90% abundance)
• Allows for lesion dosimetry,
• better quantitation of uptake with PET
&
half life 4.2 days
• Not FDA approved for routine use
• Clinical trial use of the product requires filing of an investigator-sponsored
Investigational New Drug (IND) application to the FDA.
• Can be produced in cyclotron, but is volatile and contaminates cyclotron
• Can be ordered from IBA molecular
PET/CT
F18-DOPA - Best
Radiopharmaceutical for
Medullary Thyroid Cancer
• F18-Dopa (6-L-F18-fluorodihydroxyphenylalanine)
• Precursor of dopamine and other catecholamines
•
•
•
up-regulation of amino acid transporters for large amino acids like phenylalanine and tyrosine
affinity for amino acid decarboxylase
accumulation in monoamine storage vesicles
• Used in brain research studies &
• neuroendocrine tumors & congenital hyperinsulinism
Not FDA approved for routine use in US
requires IND application to FDA
33
5/8/2015
PET/CT
PET/CT Imaging of the
Medullary Thyroid Cancer
• 18F-FDOPA - best radiopharmaceutical (Not FDA approved)
significant diagnostic performance if Calcitonin>150 pg/mL. *
• In negative FDOPA, FDG should be the next PET radiopharmaceutical,
especially if Calcitonin and CEA levels are rising rapidly.*
.
• PET with a somatostatin analogue labelled with gallium-68 when neither
FDOPA nor FDG PET are conclusive. * (Not FDA approved)
• Bone scintigraphy could complement FDG PET/CT if FDOPA is not
available*
What is currently the best radiopharmaceutical for the hybrid PET/CT detection of recurrent medullary thyroid carcinoma?
Slavikova K et al. Curr Radiopharm. 2013 Jun 6;6(2):96-105. Review
PET/CT
MTC (Calcitonin 260 pg/mL)
FDG
FDOPA
For well differentiated, metastatic MTC FDOPA is the best
radiopharmaceutical for PET/CT
Slide from Trond Velde Bogsrud, MD, PhD
Oslo University Hospital, Oslo, Norway, &
Aarhus University Hospital, Aarhus, Denmark
34
5/8/2015
PET/CT
Gallium 68-octreotide
PET/CT
SPECT
68Ga for PET/CT imaging
111
In for SPECT imaging
DOTA or DTPA
a chemical link between the
peptide and the radionuclide
NET – unknown primary
Gabriel, M., et al., JNM 2007
Somatostatin analogue
Much better resolution than In111-Octreotide
Gallium 68 - positron emitter
• Mean positron range in tissue 2.24 mm (not ideal)
• Half life 68 min
• Comes from Ge-68/Ga-68 Generator
(made in Germany and Russia) Parent 68Ge half life - 271 days
PET/CT
Ga68-octreotide
• Not FDA approved for routine use, requires IND
• Used for medullary cancer in Europe, but FDOPA better
• May have increased role when Lu177- octreotide approved for therapy in US
(current multicenter phase III trial)
• Medullary thyroid cancer - somatostatin avidity prior to therapy
• Differentiated thyroid cancer - somatostatin avidity
*Differentiated thyroid cancer: a new perspective with radiolabeled somatostatin
analogues for imaging and treatment of patients. Versari A, et al.Thyroid. 2014.
SSTR imaging provided positive results in more than half of the
cases with radioiodine- negative DTC, and about one third
ofpatients were eligible for PRRT*
TG positive Radioiodine scan negative patient with papillary thyroid cancer**
**Kundu P et al Eur J Nucl Med Mol Imaging 2014; 41: 1354-1362.
35
5/8/2015
36