Biomed Imaging Interv J 2006; 2(4):e56
© 2006 Biomedical Imaging and
Clinical use of PET/CT in thyroid cancer diagnosis and management
FX Sundram*, MBBCh, DMRT
Nuclear Medicine and PET/CT Centre, Subang Jaya Medical Centre, Subang Jaya, Selangor, Malaysia
The incidence of thyroid cancer is low, but when it occurs,
it is mainly of the papillary histopathological type. Although PET/CT has a
limited role in the diagnosis, it plays a significant role in the overall
post-surgery management of a patient with thyroid cancer. This follow-up role
is important, especially in patients with elevated serum thyroglobulin, but
negative radioiodine whole body scans. There is increasing evidence that PET/CT
should be a part of routine care in the Tg positive Radioiodine scan negative
patient. � 2006 Biomedical Imaging and Intervention Journal. All rights
Keywords: Thyroid cancer, thyroglobulin, radioiodine
Thyroid cancer is an uncommon disease, with a yearly
incidence of about 40 out of 100,000 in women and 15 out of 100,000 in men. The
majority of thyroid cancers are of the differentiated type, mainly papillary,
and to a lesser extent follicular cancer. For early diagnosis of thyroid
cancer, Ultrasonography and fine-needle aspiration biopsy of thyroid nodules is
important. Scanning with Tc-99m pertechnetate, Tc-99m sestamibi or tetrofosmin
and Thallium-201 Chloride, may help in some cases . The use of 18 F-
fluorodeoxyglucose to assess thyroid nodules is still under consideration .
Choi et al  found focal thyroid lesion in 4% of PET/CT scans, with maximum
SUV of malignant thyroid lesions to be significantly higher than that of benign
lesions. The cancer risk of focal thyroid lesions was found to be 39%.
Age, sex, tumour stage, and histopathological grading have
prognostic significance. Total thyrodectomy is the treatment of choice for
differentiated thyroid cancer, and the procedure includes lymph-node dissection
of the central compartment. Radioiodine treatment usually follows
thyroidectomy, to ablate benign thyroid remnants and destroy remaining
malignant cells. Follow-up with serum thyroglobulin levels, sonography of the
thyroid bed, and radioiodine scintigraphy is essential, especially to detect
local recurrence or distant metastases . There is good correlation between
the Tg levels (in the absence of thyroglobulin autoantibody) and persistence of
disease. In most cases, undetectable Tg levels suggest absence of either
thyroid tissue or distant metastases [4,5]. An elevated serum Tg suggests
disease and is usually associated with an abnormal I-131 WBS, with either local
recurrence or distant metastases. However, discordant results between I-131 WBS
and serum thyroglobulin have been encountered. In particular, approximately 15
to 20% of patients with high serum Tg have negative I-131 diagnostic WBS [5,6].
These false-negative scans may be due to the low dose of iodine administered
(diagnostic dose), presence of tumour deposits too small to be detected by a
gamma camera, or loss of iodine concentration as a result of tumour
dedifferentiation, with impaired sodium-iodide symporter (NIS) system or
impaired TSH receptor stimulation. Several recent studies have shown that
fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) can be
used to detect local recurrence and distant metastases of thyroid carcinoma,
especially in those patients who present with high serum Tg, but negative I-131
Serum Thyroglobulin (Tg) and Radionuclide scans in the
follow-up of differentiated thyroid cancer (DTC)
The follow-up of patients treated for DTC usually includes
clinical monitoring, serum thyroglobulin measurements, radionuclide imaging, and
anatomic imaging (ultrasonography and CT scans) when indicated. Both Tg
measurements and radionuclide imaging rely on TSH stimulation for higher
sensitivity. The serum Tg under TSH stimulation (after stopping thyroid hormone
for four to six weeks or after two intramuscular injections of recombinant TSH
(rhTSH)) is a good indicator of persistent or recurrent disease . The Tg
level is reliable only if Tg antibodies are undetectable and recovery of Tg is
in the normal range. If high-risk and low-risk groups are differentiated, the
consensus is that for low-risk group in complete remission, ultrasonography of
the neck and rhTSH stimulated Tg are sufficient for further follow-up .
For high-risk patients, many centres perform radioiodine
I-131 scans, with Tg under TSH stimulation. The specificity of I-131 whole body
scans (WBS) is high, but the sensitivity is low . Radioiodine therapy
necessitated by rising Tg levels has a therapeutic effect, and the post-therapy
WBS has a higher sensitivity compared with a low-dose diagnostic scan . In
some patients, there is elevation of TSH-stimulated Tg, but the diagnostic
I-131 WBS is negative. Explanations for false negative WBS could be iodine
contamination, insufficient TSH stimulation, small tumour volume, or iodine
negative metastases . FDG PET/CT should be considered if the last two
reasons are likely. Other tracers, such as, Technetium-99m sestamibi may be
used for WBS, especially for soft tissue/nodal disease .
PET/CT in the follow-up of thyroid cancer
Using FDG-PET imaging Feine et al.  noted that
differentiated tumours with iodine avidity have low glucose metabolism in most
patients, with the converse also being true, indicating that high glucose
metabolism signifies poor tumour differentiation and higher possible malignant
potential. The diagnostic sensitivity of FDG-PET and I-31 WBS combined was
found to be 95%. I-131 negative, but FDG-positive or I-131 positive and FDG
negative scan was found in 90% of the patients. Examples of this �flip-flop�
phenomenon are shown in Figure 1 and Figure 2.
Figure 1 I-131 positive scan with negative
Figure 2 Negative I-131
scan in patient with lung metastasis on CT and PET scans.
FDG-PET has been advocated as a monitoring procedure for
- High-risk disease
- Adverse histology (e.g., columnar cell, tall cell, and insular variants)
- Rising Tg levels with no known anatomic source
- Hurthle cell carcinoma
FDG-PET has also been recommended for post-treatment
response assessment, lesion dosimetry, and evaluation of the thyroid nodule,
but not recommended for determining extent of disease in low-risk cases.
FDG-PET scans are most useful in �high-risk� patients,
wherein tumours are more biologically aggressive, and for metastatic disease. Apart
from aiding in diagnosis, PET measurement of glucose metabolism provides biologic
information, as noted in the standardised uptake value (SUV). Patients whose
cancers take up FDG well are not likely to respond to radioactive iodine. Furthermore,
the PET-FDG SUV is a strong predictor of adverse prognosis, with higher SUV�s
indicating worse overall prognosis .
The usefulness of FDG-PET may depend on factors, such as, Tg
level, TSH stimulation by thyroid hormone withdrawal, and TSH stimulation by
rhTSH administration. In a study by Schluter et al , positive FDG-PET scan
results were achieved in 11% of patients with Tg levels of 10ng/ml or less;
this increased to 50% among patients with Tg levels between 10 to 20 ng/ml and
to 93% at Tg levels above 100ng/ml.
Patients should generally stop thyroid hormone treatment
prior to PET scanning. TSH stimulation could be either via hormone withdrawal
or by injection of rhTSH. In a study by Petrich et al , the sensitivity of
FGD-PET was 53% during TSH suppression and 87% following rhTSH stimulation.
Their conclusion was that rhTSH FDG-PET suggested specific therapeutic
interventions in 57% of patients, with surgery indicated in 23%.
With the introduction of PET/CT imaging for cancer,
questions arise as to whether PET/CT imaging is superior to PET and CT alone,
and does PET/CT improve patient management compared with both modalities alone.
PET can be considered functional (metabolism), while CT mainly reflects
anatomy. In combined PET/CT the CT data are used for attenuation correction and
anatomic localisation. There is no consensus yet on whether the CT should be
done as contrast-enhanced diagnostic CT or as low-dose CT for anatomic
correlation. Generally the PET/CT scans are done without contrast, as the SUV
values are altered by contrast, which also reduces I-131 uptake when the
treatment dose is given. Early clinical results of PET/CT fusion imaging
indicate that the exact localisation of hypermetabolic lesions leads to better
reliability of results and higher diagnostic confidence, compared with each
imaging modality alone [18,19]. In general, for staging and restaging of
various tumours, there is additional information in about 45% of patients and
change in management in 15% of patients using PET/CT fusion imaging . Furthermore,
pitfalls of PET, such as, normal structures in head and neck region, bowel
activity, muscle activity, renal excretion, ureteric activity, and brown fat
tissue could be reduced by using PET/CT .
In our study of thyroid cancer patients with elevated Tg,
but negative I-131 WBS, lesions were found in 15 out of 17 patients consistent
with metastases, resulting in 88% sensitivity . Nahas et al  report a
PET/CT sensitivity of 66% in identifying recurrent disease, with a specificity
of 100% and a positive predictive value of 100%. These authors conclude that
PET/CT is most useful in the detection and the management of recurrent
papillary thyroid carcinoma in patients with average Tg levels greater than
10ng/ml. A more recent study by Palmedo et al  using PET/CT in patients
with suspected iodine-negative differentiated thyroid carcinoma, showed
diagnostic accuracy of 93% for PET/CT and 78% for PET alone. They also noted
that in tumour positive PET patients, the PET/CT fusion imaging led to a change
of therapy in 48% of the patients.
The Centres for Medicare and Medicaid Services (USA) began
coverage of FDG-PET procedure in October 2003, for restaging of recurrent or
residual thyroid cancer of follicular cell origin that has previously been
treated by thyroidectomy and radioiodine ablation in patients with serum Tg
levels of 10ng/ml or greater and negative I-131 WBS.
Early this year, the American Thyroid Association produced
an excellent set of Management Guidelines for patients with thyroid nodules and
differentiated thyroid cancer . They recommended that if an empiric dose
(100 to 200 mCi) of radioiodine fails to localise persistent disease, FDG-PET
should be considered, especially in patients with unstimulated serum
thyroglobulin levels more than 10 to 20 ng/ml.
Iodine-124 produced in a clinical cyclotron facility can be
used to identify mediastinal micrometastases in thyroid carcinoma .
Freudenberg et al  reported that Iodine-124 PET/CT imaging is a promising
technique to improve treatment planning in thyroid cancer. It appears likely
that I-124 PET/CT may have an important role for individualised dosimetry in
patients with metastatic thyroid cancer . Although I-124 is available in
only a few hospitals worldwide, it is an ideal tracer for dosimetry. The
treatment dose with Iodine -131 can be planned based on the dosimetric studies
done with PET/CT using I-124, especially because the spatial resolution of the
PET camera is better than the gamma-camera images using I-131 (Divgi, personal
Sundram FX, Mack P. Evaluation of thyroid nodules for malignancy using 99Tcm-sestamibi. Nucl Med Commun 1995;16(8):687-93.
Mitchell JC, Grant F, Evenson AR, et al. Preoperative evaluation of thyroid nodules with 18FDG-PET/CT. Surgery 2005;138(6):1166-74; discussion 1174-5.
Choi JY, Lee KS, Kim HJ, et al. Focal thyroid lesions incidentally identified by integrated 18F-FDG PET/CT: clinical significance and improved characterization. J Nucl Med 2006;47(4):609-15.
Sherman SI. Thyroid carcinoma. Lancet 2003;361(9356):501-11.
Menendez Torre E, Lopez Carballo MT, Rodriguez Erdozain RM, et al. Prognostic value of thyroglobulin serum levels and 131I whole-body scan after initial treatment of low-risk differentiated thyroid cancer. Thyroid 2004;14(4):301-6.
Baudin E, Do Cao C, Cailleux AF, et al. Positive predictive value of serum thyroglobulin levels, measured during the first year of follow-up after thyroid hormone withdrawal, in thyroid cancer patients. J Clin Endocrinol Metab 2003;88(3):1107-11.
Wang W, Macapinlac H, Larson SM, et al. [18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography localizes residual thyroid cancer in patients with negative diagnostic (131)I whole body scans and elevated serum thyroglobulin levels. J Clin Endocrinol Metab 1999;84(7):2291-302.
Pacini F. Follow up of differentiated thyroid cancer. Eur J Nucl Med 2002;(suppl 2):S492-6.
Schlumberger M, Berg G, Cohen O, et al. Follow-up of low-risk patients with differentiated thyroid carcinoma: a European perspective. Eur J Endocrinol 2004;150(2):105-12.
Filesi M, Signore A, Ventroni G, et al. Role of initial iodine-131 whole-body scan and serum thyroglobulin in differentiated thyroid carcinoma metastases. J Nucl Med 1998;39(9):1542-6.
Pace L, Klain M, Albanese C, et al. Short-term outcome of differentiated thyroid cancer patients receiving a second iodine-131 therapy on the basis of a detectable serum thyroglobulin level after initial treatment. Eur J Nucl Med Mol Imaging 2006;33(2):179-83.
Ma C, Kuang A, Xie J, et al. Possible explanations for patients with discordant findings of serum thyroglobulin and 131I whole-body scanning. J Nucl Med 2005;46(9):1473-80.
Ng DC, Sundram FX, Sin AE. 99mTc-sestamibi and 131I whole-body scintigraphy and initial serum thyroglobulin in the management of differentiated thyroid carcinoma. J Nucl Med 2000;41(4):631-5.
Feine U, Lietzenmayer R, Hanke JP, et al. Fluorine-18-FDG and iodine-131-iodide uptake in thyroid cancer. J Nucl Med 1996;37(9):1468-72.
Larson SM, Robbins R. Positron emission tomography in thyroid cancer management. Semin Roentgenol 2002;37(2):169-74.
Schluter B, Bohuslavizki KH, Beyer W, et al. Impact of FDG PET on patients with differentiated thyroid cancer who present with elevated thyroglobulin and negative 131I scan. J Nucl Med 2001;42(1):71-6.
Petrich T, Borner AR, Otto D, et al. Influence of rhTSH on [(18)F]fluorodeoxyglucose uptake by differentiated thyroid carcinoma. Eur J Nucl Med Mol Imaging 2002;29(5):641-7.
Burger I, Gorres G, von Shulthess G, et al. PET/CT : diagnostic improvement in recurrent colorectal carcinoma compared to PET alone. Radiology 2002;225:S424.
Schoder H, Erdi YE, Larson SM, et al. PET/CT: a new imaging technology in nuclear medicine. Eur J Nucl Med Mol Imaging 2003;30(10):1419-37.
Lind P, Kohlfurst S. Respective roles of thyroglobulin, radioiodine imaging, and positron emission tomography in the assessment of thyroid cancer. Semin Nucl Med 2006;36(3):194-205.
Ong SC, Ng DC, Sundram FX. Initial experience in use of fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography in thyroid carcinoma patients with elevated serum thyroglobulin but negative iodine-131 whole body scans. Singapore Med J 2005;46(6):297-301.
Nahas Z, Goldenberg D, Fakhry C, et al. The role of positron emission tomography/computed tomography in the management of recurrent papillary thyroid carcinoma. Laryngoscope 2005;115(2):237-43.
Palmedo H, Bucerius J, Joe A, et al. Integrated PET/CT in differentiated thyroid cancer: diagnostic accuracy and impact on patient management. J Nucl Med 2006;47(4):616-24.
Freudenberg LS, Antoch G, Gorges R, et al. Combined PET/CT with Iodine-124 in diagnosis of mediastinal micrometastases in Thyroid Carninoma. The Internet Journal of Radiology 2002;2(2).
Freudenberg LS, Antoch G, Jentzen W, et al. Value of (124)I-PET/CT in staging of patients with differentiated thyroid cancer. Eur Radiol 2004;14(11):2092-8.
Sgouros G, Kolbert KS, Sheikh A, et al. Patient-specific dosimetry for 131I thyroid cancer therapy using 124I PET and 3-dimensional-internal dosimetry (3D-ID) software. J Nucl Med 2004;45(8):1366-72.
Singer PA, Cooper DS, Daniels GH, et al. Treatment guidelines for patients with thyroid nodules and well-differentiated thyroid cancer. American Thyroid Association. Arch Intern Med 1996;156(19):2165-72.
|Received 3 August 2006; received in revised form 28 September 2006; accepted 30 December 2006
Correspondence: Subang Jaya Medical Centre, 1,
Jalan SS12/1A, 47500, Subang Jaya, Malaysia. Tel.: +603-5630
6383; Fax: +603-5633 5910; E-mail: email@example.com
Please cite as: Sundram FX,
Clinical use of PET/CT in thyroid cancer diagnosis and management, Biomed Imaging Interv J 2006; 2(4):e56
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