University of Groningen

Medullary Thyroid CarcinomaVerbeek, Hans

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Chapter 5

PET Imaging in thyroid carcinoma

Hans H.G. Verbeek, Ha T.H. Phan, Adrienne H. Brouwers

Klaas P. Koopmans, Thera P. Links

Methods of Cancer Diagnosis, Therapy and Prognosis. Vol. 7. Editor: M.A. Hayat. Springer

Sience + Business Media BV 2010.

Chapter 5

74

Introduction

Thyroid cancer is the most common endocrine malignancy. It is divided in several types with

papillary, folliculary, and Hürthecell cancer (also called differentiated thyroid cancer)

originating from the follicular epithelial cells as the most common types (>90%). Other types

are medullary thyroid carcinoma (a neuroendocrine tumour originating from the calcitonin

producing C-cells) (3%-10%) and anaplastic carcinoma (often a dedifferentiated form of the

other types) (2%-10%).1

There is a different treatment for each of these types of thyroid cancer. In differentiated

thyroid cancer the initial therapy is total thyroidectomy with or without lymph node

dissection, followed by adjuvant radioactive iodine therapy. Radioactive iodine therapy with 131I can be used successfully due to the active uptake of iodine in tumour cells of thyroid

origin. However, this property can be lost during dedifferentiation, which limits the use of this

therapy in anaplastic carcinoma. Medullary thyroid tumour cells show no iodine uptake at all

and curative options are therefore mainly limited to surgical resection of primary tumour and

metastases.2

The prognosis for differentiated thyroid cancer is good, with an average 10-years survival

between 80% and 95%. However, these tumours can dedifferentiate, which results in limited

therapeutic options, leading to a much poorer prognosis with a 5-years survival of 30%.

Medullary thyroid carcinoma has a 10-years survival of 20%-70%, and for anaplastic thyroid

carcinoma the median survival is 2-6 months.3-5

Imaging is especially important in determining the right therapeutic approach for patients

with differentiated and medullary thyroid carcinoma. Different imaging techniques are

available such as computed tomography (CT), magnetic resonance imaging (MRI),

conventional nuclear scintigraphy, positron emission tomography (PET), etc.. While MRI and

CT are imaging techniques which show morphologic structures, PET imaging depicts

pathophysiological processes and is described as functional imaging. The value of PET

imaging is emerging mainly in the follow-up of thyroid cancer. Several PET imaging

techniques are available for different types of thyroid cancer and these techniques and their

applications are discussed in this chapter.

PET imaging in thyroid carcinoma

75

Positron Emission Tomography

Positron emission tomography imaging is a technique used in nuclear medicine which is

based on the use of positron emitting isotopes in specific molecules which are relevant for

specific metabolic pathways. The PET technique yields a high resolution and the capability to

quantify the amount of radioactivity measured in a specific region. Positrons, emitted by an unstable atom nucleus, are the antiparticles of electrons and have

the same mass, but an opposite charge. Positrons are not detected by a PET camera, but

photons, which are formed when a positron fuses with an electron, are detected. This means

that the positron binds with an electron to form a positronium which annihilates. In this

annihilation process all the mass is converted into energy by which two photons are formed.

These photons, always carrying an energy of 511 keV, are emitted in opposite directions

under an angle of 180º and are detected by the PET camera.6

Radioisotopes used in PET imaging usually have a short half live, such as carbon-11(11C;

half-life (T½) 20 min), nitrogen-13 (13N; T½ 10 min), oxygen-15(15O; T½ 2 min) and fluorin-

18(18F; T½ 110 min). Positron emitting radionuclides are in most cases produced by

bombarding the target material with highly accelerated particles (deuterons or protons) using

a cyclotron and inducing a nuclear reaction. Centres which use isotopes with a very short half-

life, such as 15O, 13N, and 11C, need to have an on-site cyclotron. Other longer living isotopes

can be made elsewhere and then transported to the PET imaging facility.7

A cyclotron is a type of particle accelerator which accelerates charged particles using a

high-frequency, alternating voltage. A perpendicular magnetic field causes the particles to

assume a circular orbit so that they reencounter the accelerating voltage many times. When

the particles are accelerated fast enough they are bombarded on to specific atoms and

radionuclides are formed. These radionuclides are trapped and transported to the laboratory

where they can be processed for clinical use. The resulting end-products are called

radiotracers. The most commonly used tracers are precursors for metabolic pathways,

although many other tracer types exist. After preparation and careful quality monitoring,

tracers can be injected.

The imaging device used is the PET camera. Most PET cameras consist of a ring of special

detectors which are well suited for the detection of 511 keV gamma rays. Software registers

only simultaneously entering photonpairs on different detectors. This is called coincidence

detection. Coincidence detection removes the need for a lead collimator such that the

Chapter 5

76

sensitivity of the PET imaging system is much higher than for the conventional Anger camera

that is used in planar nuclear imaging or single photon emission computed tomography

(SPECT). Both the specific block detector structure and the absence of a collimator contribute

to a higher resolution as compared with SPECT. Another advantage of PET is that the amount

of radioactivity injected in the body can be quantitatively determined. PET is a non-invasive,

sensitive imaging tool for depicting of molecular and biochemical processes without changing

its physical properties.6

In contrast to radiologic imaging which shows the morphologic structures, nuclear

medicine techniques depict pathophysiological processes and are also described as functional

imaging methods. The imaging with PET is considered to be an useful diagnostic tool for the

detection of cancer, brain diseases, and coronary artery diseases.

Combined PET/CT

The combination of PET and CT scanning is a new promising imaging technique. The

integrated PET/CT scanner allows acquisition of CT and PET images in one session. The

combination of morphologic and functional imaging leads to more precise anatomical

localization of tumour lesions. The localization of tumour foci is important for initiating the

appropriate treatment such as surgery. Especially in patients with a negative radioiodine scan

where surgery is the only therapeutic option, the integrated PET/CT scan can be helpful in

guiding therapeutic management.

18Fluorine-fluorodeoxyglucose (

18F-FDG) PET

Mechanism

Fluorodeoxyglucose (FDG) is a glucose analogue and is used as a precursor for glucose

metabolism. In both benign and malignant tissue it enters the cell by the same glucose

transporters. However, the need for glucose in malignant cells is strongly increased because

these cells have a considerably less efficient energy metabolism.8 For example, the energy

production per molecule of glucose in malignant cells is decreased because anaerobic

glycolysis is strongly increased instead of the much more efficient energy production from the

citric acid cycle. This inefficient use of glucose is the basis for the preferential uptake of

glucose or an offered glucose analogue as FDG in malignant cells.

PET imaging in thyroid carcinoma

77

In the cell FDG is phosphorylated by a hexokinase enzyme into FDG-6 phosphate which,

in contrast to glucose-6-phospate, cannot be further metabolized. Therefore, the FDG-6-

phosphate does not leave the cell and becomes trapped intracellulary. The final quantity of

FDG-6-phosphate is proportional to the glycolytic rate of the cell. Besides the increased

glycolysis, it has been demonstrated that in malignant cells levels of transmembrane glucose

transporters (e.g., the GLUT-1 transporter) and possibly some hexokinase isoenzymes are also

increased, also resulting in increased FDG uptake.9

However, in all metabolically active tissues, such as brain cells, active muscles, and

activated macrophages, increased glucose metabolism leads to an increased FDG uptake. 18F-

FDG PET is, therefore, a marker for glucose metabolism in general. In most normal tissues

(e.g., liver, kidney, intestine, muscle and some tumour cells) the level of phosphate activity is

variable; nevertheless, FDG-6-phospate accumulation is lower than in malignant tissues. In

addition, some benign tissues require more glucose.10,11 So, the uptake mechanism of FDG

with irreversible trapping in malignant tissue is ideal for PET imaging and has been applied

widely in oncology. However, it is important to make a correct interpretation of these PET

images, for non-malignant tissue also has FDG uptake.

Scan method

Uptake of 18F-FDG occurs rapidly after administration and the amount taken up increases

with time. The most applied imaging moment is 60-90 min after tracer administration. The

reason is that the excretion of 18F-FDG via the kidneys reduces 18F-FDG in the blood, which

causes clearance of ‘background’ uptake and the decay of fluorin-18 (T½ 110 min). Generally

the patient preparation consists of an 18F-FDG injection in a fasting condition and after oral

prehydration. The injected dose varies between 2-8 MBq/kg.

Clinical application

Thyroid nodules

The value of 18F-FDG PET in the distinction between malignant and benign thyroid nodules

before surgery is unclear. Several studies reported that 18F-FDG PET is useful in the

preoperative evaluation of cytologicaly inconclusive nodules with a high negative predictive

value.12-14 De Geus-Oei et al. observed that the probability for thyroid cancer increased from

14% (pre-PET) to 32% (post-PET) in case the nodule was positive on 18F-FDG PET.12 In this

study 18F-FDG PET could reduce the number of futile hemithyroidectomies by 66%.

Chapter 5

78

A. 18F-FDG PET

B. CT-lung C. 18F-FDG PET/CT

Figure 1 These are the images of a 68-year old male known with follicular thyroid cancer. This patient showed

increased serum Tg level (14 ng/ml) suspected for recurrent or metastatic disease. Blind treatment with 131

I

was given followed by a post-treatment whole body scan (WBS) after 10 days which was negative. 18

F-FDG PET

(A) showed a focal lesion in the lower lobe of the left lung (arrow), confirmed by CT (B, arrow). Picture C

showed the fusion image of 18

F-FDG PET and CT for the lesion in the left lung (arrow).

However, recent studies by Kim et al. and Bogsrud et al., demonstrated that 18F-FDG PET is

not helpful in differentiating between malignant and benign nodules, and therefore has only

limited value in preoperative evaluation of indeterminate thyroid nodules.15,16

So, conflicting results are reported on the usefulness of 18F-FDG PET in the prediction of

malignancy in thyroid nodules in case of inconclusive cytology, and therefore further research

is needed. Meanwhile histopathological examination remains the gold standard.

Differentiated thyroid cancer (DTC): follow-up

More information is available regarding the value of 18F-FDG PET in the follow-up of thyroid

cancer such as the detection of recurrences or metastases, especially in patients with a

negative radioiodine scan or in patients who has lost the ability to accumulate iodine. A

PET imaging in thyroid carcinoma

79

complementary uptake of 18F-FDG and radioiodine can be present, which is known as the

‘flip-flop’ phenomenon and was first described by Joensuu and Ahonen.17 This phenomenon

might be explained by the degree of tissue differentiation. Well differentiated thyroid tissue

has the capability to take up iodine but is metabolically inactive while less differentiated

thyroid cancer tissue loses its capability to trap iodine and becomes metabolically more

active. This makes 18F-FDG PET scanning the method of choice for the detection of 131I

negative metastases of differentiated thyroid carcinoma.18

Performance of 18F-FDG PET during thyrotropin (TSH) stimulation improves the results in

comparison to the scanning during the euthyroid state (during thyroxin treatment) as was

shown by van Tol et al..19 In vitro studies have shown a stimulating effect of TSH on Glut 1

expression and glucose transport.20,21 This increase in glucose carriers results in a higher

uptake of glucose and also 18F-FDG in thyroid cancer cells, which improves the result of the

PET-scan. Stimulation with exogenous TSH (recombinant human(rh) TSH) also increases 18F-FDG uptake by differentiated thyroid cancer, and therefore more lesions can be detected

and tumour/background contrast is enhanced.22,23 The influence of rhTSH on the background

is not well-known, but there is evidence that rhTSH increases 18F-FDG uptake in the tumour

lesion itself.

Several studies have been performed to assess the value of 18F-FDG PET imaging in the

follow up of thyroid cancer. Hooft et al. performed a meta-analysis of studies that investigated

the role of 18F-FDG PET in patients with thyroid cancer after negative radioiodine

scintigraphy and elevated serum thyroglobulin.24 The diagnostic accuracy of these studies was

assessed. Observed sensitivity and specificity in these studies were ranging from 70%-95%

and 77%-100%, respectively. Furthermore, they observed that there are methodological

problems in these studies such as small sample size, validity of reference tests, and short

follow-up. Nonetheless, 18F-FDG PET is now considered a valuable diagnostic imaging tool

in the follow-up of 131I-negative patients for the detection of recurrences or metastases.

However, it is not known whether PET is superior to bone scintigraphy in the detection of

bone metastases in thyroid cancer. Comparative studies of bone scans and 18F-FDG PET are

lacking. In a retrospective study, 24 patients had undergone both 18F-FDG PET and bone

scans within six months because of suspected bone metastases.25 This study shows that bone

scintigraphy is still valuable in differentiated thyroid cancer, as it was found that 38% of bone

metastases could be missed on 18F-FDG PET. Further prospective studies in a higher number

of patients are required to define the exact role of bone scan and 18F-FDG PET in the

detection of bone metastases in patients with differentiated thyroid cancer (DTC).

Chapter 5

80

Combined or integrated 18F-FDG PET/CT in patients with negative 131I scans and elevated

thyroglobulin (Tg) showed that the diagnostic accuracy can be improved compared to 18F-

FDG PET or CT alone. The combination of these imaging techniques has also led to a change

in patient management and therapy, e.g., extension of surgery by providing precise anatomical

localization of the recurrent or metastatic disease.26

Medullary thyroid cancer (MTC)

The detection of recurrence or metastases in MTC is difficult and there is no single method

sensitive enough to reveal all MTC recurrences or metastases. In comparison with the

calcitonin tumour marker nearly all imaging modalities (Ultrasonography, CT, MRI, and

scintigraphy) have limited sensitivities. The clinical role of 18F-FDG PET in the diagnosis and

staging of recurrent and metastatic MTC seems promising.27

The sensitivity and specificity of 18F-FDG PET ranges between 73%-88% and 76%-80%,

respectively. In a study by de Groot et al., 18F-FDG PET was performed in patients with

elevated serum tumour markers after total thyroidectomy.28 Compared with 111In-octreotide

imaging(lesion based sensitivity: 41%), 99mTc(V)DMSA scintigraphy (57%) and

morphological imaging (87%), 18F-FDG PET (96%) was superior. However, morphological

imaging will always be needed because 18F-FDG PET only yields functional data and no

morphological information, which is necessary to assess resectability.

The combination of 18F-FDG PET/CT can have a useful role in medullary thyroid cancer.

Because surgery only can cure the disease, precise anatomical localization and the extent of

the recurrent or metastatic disease is mandatory. However, little data and case reports have

shown an increased diagnostic accuracy so further studies are needed.27

18Fluorine-dihydroxyphenylalanine (

18F-DOPA)

Mechanism

The mechanism responsible for uptake of 18Fluorine-dihydroxyphenylalanine (18F-DOPA) in

medullary thyroid carcinoma is probably the strongly upregulated transmembrane transport of

amino acids via the large amino acid transporters in medullary thyroid carcinoma cells. It is

not yet clear whether the increased uptake of 18F-DOPA PET is the result of the increased

transporter capabilities or the increased metabolic activity of the catecholamine pathway.

PET imaging in thyroid carcinoma

81

After transmembrane transport, 18F-DOPA is intracytoplasmatically converted into

dopamine by the enzyme aromatic acid decarboxylase (AADC). The formed 18F-dopamine is

transported into secretory vesicles via the vesicular mono aminoacid transporters (VMAT) in

which it can be further metabolized to 18F-noradrenalin and 18F-adrenalin.29 Although the 18F

atom influences the metabolism of 18F-DOPA there is no or little effect on the transport into

the intracellular environment. In the kidneys, 18F-DOPA is rapidly converted into 18F-dopamine

which is than excreted actively in urine. This conversion can be inhibited by oral

administration of carbidopa prior to tracer administration.30

Carbidopa also lowers the physiological uptake of 18F-DOPA in the pancreas, but it is yet

unknown which mechanism is responsible for this decrease in pancreatic uptake. The

reduction in renal and urinary activity leads to a better image quality in the surroundings of

the urinary system. Also, the reduced uptake in the pancreas makes the identification of

lesions in the pancreatic region easier. It can be speculated that by reducing the excretion of 18F-DOPA, more 18F-DOPA is available for neuroendocrine tumour lesions; thereby,

increasing the tumour to background ratio, leading to a better discrimination of

neuroendocrine lesions.

Scan method

In most centres, patients are prepared with oral administration of carbidopa, either in a fixed

dose or in a dose calibrated to body weight. Patients are scanned in a fasting condition for 4-6

h. In most centres a whole body study will be performed ranging from the skull to the upper

femora. The average injected dose is 200 MBq, the radiation burden ~ 4 mSv.30 Attenuation

correction is applied, either by using a CT in a PET-CT machine or by using camera-specific

attenuation protocols.

Clinical application

Medullary thyroid cancer

Although 18F-DOPA PET is not yet in widespread use, it is a promising new functional

imaging procedure for imaging neuroendocrine tumours. More and more centres gain access

to this tracer either via on-site production or production elsewhere. Hoegerle et al. were the

first to describe the use of 18F-DOPA PET in medullary thyroid cancer.31 In this study 18F-

DOPA PET was compared with 18F-FDG PET, SRS, and CT/MRI. A high precision of 18F-

DOPA PET was observed in the diagnosis of lymph node metastases (sensitivity 88%), while

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82

organ metastases were better detected with conventional imaging (sensitivity 13%). In the

recently published study by Koopmans et al. diagnostic accuracy was assessed for 18F-DOPA

PET in patients with carcinoid tumours which are, like medullary thyroid carcinoma,

neuroendocrine tumors.32 Compared to conventional somotostatine receptor scintigraphy

(SRS) they showed improved sensitivity of 18F-DOPA PET in staging and identify carcinoid

tumours.

A. 18F-FDG PET B. 18F-DOPA PET

Figure 2 These are the images of a patient known with medullary thyroid cancer. In this patient 18

F-FDG PET

(A) and 18

F-DOPA PET (B) were performed. The 18

F-DOPA PET (B) showed multiple lesions in the liver and

several lesions in the spinal column(arrows) while the 18

F-FDG PET showed hardly any lesions.

The value of 18F-DOPA PET for the detection of recurrent or residual disease in 21 patients

with postsurgically elevated calcitonin or CEA was assessed by Koopmans et al..33 They

compared 18F-DOPA PET with 18F-FDG PET, 99mT(V)DMSA, and CT/MRI. 18F-DOPA PET

was superior to conventional imaging for the detection of MTC on patient (sensitivity 87%)

and regional (89%) level. On lesional level 18F-DOPA PET (sensitivity 71%) was equal to

morphological imaging (64%) but superior to 18F-FDG PET (30%) and 99mT(V)DMSA (19%).

In the recent study by Beuthien-Baumann et al., 18F-DOPA-PET also seems to be more

specific than 18F-FDG PET for the detection of metastases of MTC.34 Thus, compared with 18F-FDG PET and conventional imaging techniques, 18F-DOPA PET provides better results in

the imaging of medullary thyroid cancer. However, it is still unclear if this improved imaging

results in different therapeutic approaches, and so further research is needed.

PET imaging in thyroid carcinoma

83

11C-Methionine (MET) PET

Mechanism

Proteins play an important role in virtually all biological processes. Proteins are built from a

set of 20 amino acids. Amino acid transport across the cell membranes into the cells occurs

primarily via carrier-mediated processes. Amino acid transport is generally increased in

malignant transformation.35-37 This increased protein metabolism in cancer cells is important

for metabolic tumour imaging, for which radiolabeled amino acids can be applied. These

amino acid tracers could help in imaging areas where 18F-FDG is limited such as the

interference of high (physiologic) 18F-FDG uptake in the brain. Another reason is that amino

acid imaging is less influenced by inflammatory disease. The most frequently used

radiolabeled amino acid is L-[methyl-11C]-methionine. Normal biodistribution of radiolabeled

methionine occurs in the pancreas, liver, spleen, kidney, and salivary glands.

Scan method

11C-MET PET scanning can be performed 10 to 20 min after intravenous injection of a fixed

dose or a dose calibrated on body weight (suggested range is 70 MBq to 1100 MBq), in a

fasting condition for 2-6 h. Images are corrected, either by using a CT in a PET/CT machine

or by using camera-specific attenuation protocols.

Clinical application

Differentiated thyroid cancer

The need for new tracers and improvement of diagnostic tools in thyroid cancer is growing.

So far, no data on the application of methionine (MET) PET in thyroid cancer are available.

The general feasibility of amino acid imaging in many tumour types has been sufficiently

shown.37

It is imaginable that thyroid cancer could sufficiently concentrate amino acids due to its

metabolically inert nature and high protein synthesis (e.g., thyroglobulin). In a feasibility

study by Phan et al., 11C-MET PET has been compared with 18F-FDG PET in the detection of

recurrent or metastatic disease in 20 patients with negative 131I scans and elevated Tg.38 Six of

the 20 patients showed uptake on both PET scans, but the abnormalities were more 18F-FDG-

avid and more extensive on the 18F-FDG PET in 3 patients. In four of the 20 patients uptake

Chapter 5

84

was only observed on the 11C-MET PET; however, no anatomical localization could be

confirmed. Presently, the significance of the MET uptake in these four patients is unclear, so

the clinical value of 11C-MET PET in the detection of recurrent DTC disease still has to be

proven in the (long-term) follow-up.

A. 11C-MET PET B. 18F-FDG PET

Figure 3 These are the images of a 68-y old female known with papillary thyroid cancer. This patient had

unreliable Tg due to the presence of Tg antibodies (which were increasing in the course of the follow-up). The

post-treatment 131

I whole body scan (WBS) was negative. Due to suspicion of dedifferentiated, metastatic

disease 11

C-MET PET (A) and 18

F-FDG PET (B) were performed. 11

C-MET PET (A) showed lesions in the

mediastinum with slightly to moderate 11

C-MET uptake. 18

F-FDG PET (B) also showed multiple lesions in the

mediastinum, but the lesions showed clearly higher 18

F-FDG uptake and the abnormalities were more

extensive.

124Iodine-PET

Mechanism

Iodine-124 is a positron emitting isotope, which is suitable for PET imaging, with a half-life

of 4.2 days.39 This isotope has been used for dosimetric purposes or thyroid volume

measurements.40 While the radioisotopes 123I and especially 131I are used on a wide scale in

diagnosis and treatment of many thyroid disorders, 124I has received little attention.

Chemically identical to nonradioactive iodine, this radioisotope allows thyroid cancer imaging

with the high resolution PET technique.39,40

PET imaging in thyroid carcinoma

85

Scan method

The 124I -PET scan can be obtained 24 h to 6 days after administration of 74-100 MBq of 124I.

A whole body PET scan (from the upper thigh up until the top of the skull) can be performed

in 2D or 3D mode, using standard energy window setting of 350-650 keV (or energy window

setting 425-650 keV or 460-562 keV in case of the presence of high amounts of 131I.41

Clinical application

Differentiated thyroid cancer

Accumulation of iodine is a highly specific characteristic for differentiated thyroid cancer

(DTC) cells. In patients with increasing or recurrent detectable Tg a blind treatment (meaning

after a negative diagnostic 131I scan) with high dose 131I followed by a post-treatment 131I scan

is used as a diagnostic tool. However, this strategy with (unnecessary) high radiation exposure

must be taken into account in patients without 131I uptake in their metastases. Besides the high

radiation exposure, there is a high TSH level which potentially stimulates thyroid cancer cell

growth.

Based on the higher spatial resolution, 124I-PET is potentially able to detect recurrent

disease in DTC with a higher sensitivity than (diagnostic) 131I scans. With this higher

sensitivity and the possibility to combine the 124I-PET scan with morphologic imaging, such

as CT data, an appropriate therapeutic decision in terms of surgery and/or additional high dose 131I can be made. 124I-PET imaging might, therefore, become the diagnostic tool of choice in

the follow-up of DTC. In the study by Freudenberg et al., 124I-PET (/CT) modalities were

compared with the high dose 131I-WBS in 12 patients with DTC.42 They showed an overall

lesion detectability of 87 %, 83%, and 100% for 124I, 131I-WBS and combined 124I-PET/CT

respectively. So, these 124I-PET (/CT) modalities are promising diagnostic tools and are

suitable alternative to the high dose 131I-WBS in the follow-up of DTC patients.

In a prospective, feasibility study by Phan et al., 20 patients with advanced DTC (T4,

extranodal tumour growth, distant metastasis) underwent a low-dose diagnostic 131I scan, a 124I PET scan, and a high-dose (posttreatment) 131I scan.43 The 131I images were compared to

the 124I-PET images. 124I-PET proved to be a superior diagnostic tool as compared to low dose

diagnostic 131I scans, and showed comparable findings with the post-treatment 131I-WBS

which was in agreement with the study by Freudenberg et al. and Abdul Fatah et al..42,44

Therefore, 124I-PET could be used as a diagnostic tool in the follow-up of patients with DTC

for the favourable radiation exposure burden compared to the high dose diagnostic 131I-WBS

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86

and the superior diagnostic accuracy compared to low dose diagnostic 131I-WBS and the

fusion possibility with CT which improves clinical decision making.

A. Post-treatment 131I-WBS B. 124I-PET

C. 18F-FDG PET

Figure 4 These are the images of a 68-year old male known with follicular thyroid cancer. This patient showed

increased serum Tg level (14 ng/ml) suspected for recurrent or metastatic disease. Blind treatment with 131

I

was given followed by a post-treatment whole body scan (WBS) after 10 days (A), which was negative. The 124

I-

PET (B) was also negative, besides physiological uptake in the salivary glands, oesophagus, gastro-intestinal

tract, kidney and bladder. 18

F-FDG PET (C) showed a focal lesion in the lower lobe of the left lung (arrow),

confirmed by CT. This complementary uptake of radioiodine and 18

F-FDG is known as the flip-flop phenomenon.

Conclusion

This chapter on PET imaging in thyroid cancer gives an overview of the different PET

techniques available in thyroid cancer. PET imaging is based on two principles: the ability of

unstable atom nucleus to emit positrons and the labelling of organic molecules, which are

used in specific metabolic pathways.

PET imaging in thyroid carcinoma

87

For differentiated thyroid cancer the most frequently used PET technique is 18F-FDG PET

imaging, which is based on the use of a glucose analogue. Although its application in the

preoperative assessment of thyroid nodules is still unclear, it is considered an useful tool in

the follow up of differentiated thyroid cancer. The use of PET/CT scanning which combines

functional imaging with morphological imaging is promising, providing more accurate

localization of tumour sites, which is important for further treatment.

Other PET radiotracers have been developed: the clinical value of amino acid tumour

imaging with 11C-MET PET is unclear and still has to be proven in the follow-up of

differentiated thyroid cancer. Another relative new PET imaging technique is the iodine

isotope 124I. Compared with the high dose diagnostic 131I whole body scan, 124I-PET showed

similar findings and can therefore be used as a diagnostic tool in the follow-up of

differentiated thyroid cancer.

For the follow-up of medullary thyroid cancer 18F-FDG PET is also the most employed

imaging technique. However, 18F-DOPA PET, which is based on a precursor of dopamine,

seems to be superior compared to 18F-FDG PET in the follow up of medullary thyroid cancer.

A potential new tracer is 11C-5-HTP, which is based on a precursor of serotonin and already

has been applied in neuroendocrine tumours. The value of this technique has to be further

assessed in medullary thyroid cancer.

The need for new tracers and advanced PET imaging to improve the diagnostic

sensitivities and accuracy in detection, staging, and follow-up of thyroid cancer patients is

growing. Knowledge of the pathogenesis, the molecular characteristics and the behaviour of

the tumour cell is crucial for developing of specific tracers and techniques, e.g., radiolabeled

Tg, (rh) TSH. Although new tracers are developed and applied in patients, little data are

available on the changes in therapeutic management these new PET-techniques give. While

PET-imaging is still in development, more research is needed to assess the effects on therapy

of these new developments. In conclusion, PET imaging is a useful diagnostic tool in thyroid

cancer and new promising techniques are developed which could further improve the

diagnostic accuracy and therapeutic approaches.

Chapter 5

88

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