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S. Sen and D. T. Abraham
The Role ofNuclear Medicine inThyroid
andParathyroid Disorders
P.ShanmugaSundaram, PadmaSubramanyam,
andG.DineshKumar
16.1 Introduction toNuclear Medicine
Nuclear medicine is a subspecialty that uses medically approved radioisotopes for
imaging and therapy. Gamma-emitting radioisotopes are ideal agents for imaging,
while beta and alpha emitters are used for radionuclide therapy. Nuclear imaging is
commonly called “Scintigraphy” derived from the Latin word “scintilla,” meaning
“spark.” The gamma camera is the instrument used to acquire images (gamma emissions or scintillations), while PETCT/MR captures the gamma-ray emissions from
positron-emitting radioisotopes injected into the patient. All patients receive a
radioactive isotope/radiopharmaceutical injection, and once it gets localized into
the organ of interest, images are acquired. Processed high-quality images are visually and quantitatively analyzed to identify early organ physiological derangements.
16
16.1.1 Radiopharmaceuticals [1]
Radiopharmaceuticals are also known as radiotracers, comprising a radionuclide
and a pharmaceutical that helps in the localization of radionuclide in the organ of
interest. Generally, physiological changes precede anatomical derangements.
Therefore, nuclear imaging identies diseases much earlier than any other anatomical imaging counterpart. In the case of the thyroid,
concentrated by thyroid follicular cells because of its afnity to iodine. The
P. S. Sundaram (*)
Department of Nuclear Medicine and PET CT, Amrita Institute of Medical Sciences,
Cochin, Kerala, India
P. Subramanyam · G. DineshKumar
Department of Nuclear Medicine & Molecular Imaging, Amrita Institute of Medical Sciences,
Cochin, Kerala, India
© The Author(s), under exclusive license to Springer Nature Singapore Pte
Ltd. 2024
C. G. Nair, S. J. Abraham (eds.), Surgical Management of Thyroid and
Parathyroid Diseases, https://doi.org/10.1007/978-981-97-3774-1_16
131
I (radioiodine) gets maximally
209
210
P. S. Sundaram et al.
elemental form of iodine (stable iodine, i.e.,
127
I) is essential for producing thyroid
hormones. Hence, radioiodine is the universal radiotracer for imaging and treating
thyroid diseases.
131
Iodides or iodide analogues (
123
I or
I) are actively transported into the thyroid
gland based on the sodium iodide symporter mechanism (NIS). The NIS is an intrinsic membrane protein implicated in iodide uptake into thyroid follicular cells. As
the pure gamma-emitting
123
I is not available in India, gamma and beta-emitting
131
is predominantly used.
The main use of
131
I is to determine the functional status of the thyroid gland in
hyperthyroidism and also in the postoperative imaging and therapy of differentiated
thyroid carcinoma (DTC).
Tumor seeking radiopharmaceuticals such as
99m
Tc- SestaMIBI (
99m
Tc-MIBI)
and PET tracer like 18F- Fluorodeoxyglucose (18F FDG) may be useful in discriminating benign from malignant thyroid nodule/s.
16.1.2 Radiopharmaceuticals Used inThyroid Imaging
1. Radioactive iodine or iodine analogues (
99m
2.
Technetium (
3. Others:
131
I and
124I/18
99m
99m
TcO4 -Technetium pertechnetate)
F FDG (PET Tracers)
TcO4 are the most commonly used radiotracers for routine thyroid
imaging. Table16.1 lists the various radiopharmaceuticals used in thyroid imaging.
123I/131
I)
I
16.1.3 Radioactive Iodine (
Both
gland.
123
131
I and
124
I are gamma-emitting radioisotopes used for imaging of thyroid
I is a new PET counterpart that is still under investigation.
123I/131
I)
123
I, a pure
gamma emitter, provides better quality images with lesser radiation exposure than
131
I due to its optimum gamma energy component (159keV, kilo electron volt).
131
Both
131
I is an iodine radioisotope with gamma and beta emissions (energy of 364 and
606keV respectively). The advantages of
I and
123
I can be used for radioactive iodine uptake (RAIU) studies.
131
I are manifold:
(a) dual potential as an imaging and therapy tool
(b) selective targeting and cytotoxic effect on thyroid tissue (i.e., magic bullet—
due to selective uptake and organication in thyroid follicular cells)
(c) low cost, ready availability, oral route of administration
(d) no major side effects like hematologic, neurologic, or hepatotoxicity.
The major disadvantages of
131
I are its long physical half-life (8.02 days) and
high beta emission, leading to a relatively higher radiation dose delivery to the thyroid and longer stay in the systemic circulation.
16 The Role ofNuclear Medicine inThyroid andParathyroid Disorders
Physical
half-life
8.02 days
Time to complete
imaging
48–72 h after
oral
administration
diet for 3–4 weeks
(off Thyroxin,
Therapy
agent Pt preparation
iodized salt,
seafood, etc.)
13 h
6–8 h after IV
6 h
injection
20min after IV
diet
injection
needed
No Iodine restricted
No data No preparation No waiting time 4.02 days
110min
Post injection
waiting time of 1
h
mandatory before
FDG inj.
No data Euglycemic status
211
Use as a
diagnostic
agent
Type of emission Availability
Table 16.1 Radiopharmaceuticals commonly used in thyroid imaging
Radiotracer
Nuclear reactor Yes Ye s Iodine restricted
& beta (606 Kev)
I Both gamma (364 keV)
131
Best
imaging
tool
Yes No No preparation
available in India)
I Gamma only (159 Kev) Cyclotron produced (not
123
TcO4 Only gamma (140Kev) 24×7 available in NM
99m
tracer
dept (daily elution)
I Positron emitter Not available PET
124
18
tracer
F FDG Positron emitter Available PET
212
P. S. Sundaram et al.
Radioiodine (
131
I), also popularly referred to as “atomic cocktail,” is an ideal
therapeutic agent to treat both benign thyroid conditions such as hyperthyroidism
and malignancies like differentiated thyroid cancers.
16.1.3.1
Technetium is prepared in-house on a daily basis using a 99Mo–
99m
Technetium
99m
Tc generator
(commonly called Moly generator) by a process called elution. The nal product
eluted is Technetium pertechnetate (
99m
TcO4–).
99m
TcO4 is administered intravenously for thyroid imaging in the evaluation of hyperthyroidism/thyroid nodule
evaluation.
99m
TcO4 uptake reects only the thyroid trapping ability and not its organication ability but can nevertheless reliably differentiate various forms of
hyperthyroidism.
16.1.3.2
124
I is a cyclotron-produced PET radiopharmaceutical with a 4.2 days half-life. It
124
I Iodine
offers superior imaging characteristics with enhanced spatial resolution and higher
sensitivity.
124
I also has a favorable half-life permitting in-vivo iodine kinetics studies. It is an ideal agent for dosimetry studies in DTC.Numerous reports attest to the
potential clinical benets of
124
I imaging in patients with DTC.However, a uniform
clinical protocol for imaging, image analysis and quantitation has not yet been
rmly established.
16.1.3.3 18F Fluorodeoxyglucose, FDG
The most widely used positron-emitting radiopharmaceutical is the glucose analog FDG (Fluorodeoxyglucose) labeled with 18F (Fluorine) having a relatively
longer half-life of 110min when compared to the rest of the shorter-lived PET
agents (such as 11Carbon, 13Oxygen, etc.). Although it is not recommended as an
agent for routine evaluation of thyroid, incidentalomas can be identied during
oncologic evaluation for other malignancies. Imaging is performed using a PET
camera with either a CT or MR counterpart (PET CT/MR hybrid imaging).
FDG, being a glucose analogue, undergoes metabolism via the TCA cycle. FDG
uptake in hyperplastic or malignant cells is governed by the enhanced GLUT
(glucose transporter protein) expression. Overexpression of GLUT1in malignant cells results in increased 18F-FDG uptake. FDG is subsequently phosphorylated by hexokinase to FDG 6 phosphate. However, further metabolism of FDG
6 phosphate is curtailed and leads to its enhanced intracellular FDG accumulation. Aggressive tumors have higher FDG accumulation. This process of “metabolic trapping” of FDG in the cell constitutes the basis for imaging. It is possible
to image the entire whole body in a single session, increasing the opportunity
for nding unsuspected disease sites. Apart from oncology imaging 18FDG
radiopharmaceutical is increasingly used in the identication of sites of occult
infection in patients with pyrexia of unknown origin, prosthetic infection, epilepsy, myocarditis, myocardial viability evaluation, etc.
16 The Role ofNuclear Medicine inThyroid andParathyroid Disorders
213
16.1.4 Biokinetics ofRadioiodine
Radioiodine
131
I is available in the form of sodium iodide (NaI). It is available both as an
131
I
oral solution and capsules in different denominations that can be ordered as per requirement. Fasting for 4–6 h is recommended to enhance gastric absorption of
131
I.Once
ingested, gastrointestinal absorption is rapidly at 5% per min and 50% with 30min. The
absorption is nearly complete within 12 h. Iodine is cleared from the plasma primarily
by the thyroid gland but also by the salivary glands, gastric mucosal cells, mammary
glands (NIS mechanism), and kidneys. Maximum excretion occurs within the rst 24 h,
and the remainder is localized in the thyroid gland. Renal excretion is through glomerular ltration at a mean rate of 34 mL (milliliter) per min. Around 73% of ltered iodide
is reabsorbed by the renal tubules. Iodine is not bound in the kidneys. Renal clearance of
iodine is constant over a wide range of plasma concentrations. Although radioiodine is
not nephrotoxic, patients with renal failure should ideally undergo dialysis before the
scheduled date of high-dose
131
I administration (therapy) to reduce whole-body radia-
tion exposure (due to poor tracer clearance from systemic circulation).
16.1.5 Placental Transport andLactation
Evidence supports placental transport of radioiodine, and high fetal-to-maternal
thyroid ratios are achieved in the near term [2]. The fetal thyroid gland concentrates
131
I by the 12th–14th week of gestation [3]; hence, the use of radioiodine is strictly
contraindicated in pregnancy. Iodine accumulates in lactating breasts and is secreted
in breast milk [4]. Therefore, breastfeeding is temporarily discontinued following
123
the
I scan but may be restarted after 2–3 days. However, breastfeeding is discontinued for a minimum period of 8 weeks for those undergoing high-dose
for DTC (to achieve an infant effective dose <1mSv and an infant thyroid dose <10
mSv) [5].
131
I therapy
16.1.6 Radiation Dose toOrgans
The thyroid gland is the primary organ concentrating iodine, but the effective radiation is decided by the total uptake of the administered dose. The thyroid gland gets
the maximum dose per millicurie, approximately 1300 rad per, compared to the rest
of the body, which gets 0.71 rad.
.
16.1.7 Biokinetics of
Technetium pertechnetate behaves like iodine in the thyroid gland and is trapped
in the follicular cells within 20–30min of intravenous administration. Normally,
1–4% administered dose is concentrated in the thyroid. The maximal
99m
Tc04 (Technetium Pertechnetate)
214
P. S. Sundaram et al.
concentration of the radiopharmaceutical is seen in the gastrointestinal tract,
especially in gastric mucosa, approximately 5–10 times higher than the normal
thyroid gland. The salivary glands also accumulate technetium more than seen in
the thyroid gland. Routinely, four mCi of 99Tc pertechnetate is administered intravenously. The follicular cells tend to concentrate Group VII anions of the periodic
table that includes iodide and its analogues, i.e., pertechnetate, thiocyanate, and
perchlorate. This forms the basis of the perchlorate discharge test in congenital
hypothyroidism.
The distribution and blood clearance of
99m
Tc04 closely mimic those of iodides.
Though the preferred route of administration is intravenous, oral administration is
advisable in mentally challenged and non-cooperative patients. The material washes
off the body in 24 h through urine but is excreted in breast milk in lactating ladies.
The radiopharmaceutical crosses the placental barrier and so is generally contraindicated in pregnancy.
16.1.8 Radiation Dose toOther Organs
The amount of radiation to the thyroid gland following the routine dose of
99
Tc is similar, but the whole-body dose is marginally high 99Tc. However, both
tracers emit considerably low radiation doses to the thyroid and the body. But I
123
I and
131
,
on the contrary, emits about 100 times higher radiation in the therapeutic dosages
123
than I
. For the administered activity. (≈1rad/μCi [10mGy/0.037MBq] versus
1 rad/100 μCi [10mGy/3.7MBq]). 99Tc pertechnetate delivers 1rad/5000 mCi
(10 mGy/185 MBq) (μCi = micro curies, mGy = milligray, MBq = mega
Becquerel).
16.1.9 Placental Transport andLactation
99m
Tc crosses the placental barrier like iodine isotopes and should be avoided in
pregnant ladies since the isotopes concentrate on the fetal thyroid at about the 12th
week of gestation onwards. 99Tc is concentrated in lactating breasts and contaminates breast milk.
16.2 Thyroid Scintigraphy
Technetium thyroid scintigraphy gives valuable information regarding the anatomy
and function of the thyroid gland and is widely used in categorizing the nature of the
hyperthyroid gland.
Thyroid scintigraphy is a simple investigation to evaluate the functional status of
the thyroid gland. (Based on the selective uptake of various radionuclides by thyroid
tissue). Scintigraphy also provides valuable information on thyroid anatomy and
physiology and can play an integral role in diagnosing and managing
16 The Role ofNuclear Medicine inThyroid andParathyroid Disorders
215
hyperthyroidism. Technetium is a widely used radiopharmaceutical because of its
ease of use and reliable information. But
131
I is selectively used in specic situations
like congenital hypothyroidism along with the perchlorate discharge test.
16.2.1 Indications for
99m
TcO4 Thyroid Scintigraphy
1. Hyperthyroidism: The scintigraphy gives adequate information to differentiate a
hyperfunctioning gland from viral thyroiditis with the release of hormones due
to cellular damage. The qualitative and quantitative uptake of the tracer gives
characteristic appearances in common hyperthyroid conditions such as Graves’
disease and toxic nodular goiter toxic adenoma (Fig.16.1).
2. Scintigraphy is rarely used as part of the evaluation of the thyroid.
3. When a primary mediastinal goiter is suspected, scintigraphy helps to differenti-
ate it from other mediastinal mass lesions.
4. Scintigraphy is indicated in locating the source of hormone synthesis when
extrathyroid locations are suspected, like lingual thyroid, thyroglossal tract and
struma ovarii.
5. Congenital hypothyroidism—as a part of the assessment of native thyroid and
developmental anomalies (Fig.16.2).
6. Suspected amiodarone thyrotoxicosis (additional imaging with
99m
Tc MIBI
recommended).
7. As preliminary workup for Graves’ disease to assess the feasibility of low-dose
131
I therapy and for
131
I dose calculation.
a
c
Fig. 16.1
(a) Normal functioning thyroid gland (SG denotes salivary gland); (b) Classical Graves’ disease
with high trapping function; (c) Toxic multinodular goiter; (d) Autonomous toxic nodule of right
lobe suppressing left lobe of thyroid gland
99m
TcO4 thyroid scan showing scintigraphic uptake patterns in benign thyroid diseases.
d
b
216
P. S. Sundaram et al.
a
b
c
Lingual
thyroid
Fig. 16.2 (a)
absence of thyroid gland in its normal anatomical or ectopic positions (Myo denotes myocardium);
99m
(b)
99m
TcO4 thyroid scan showing lingual thyroid
99m
Tc MIBI thyroid scan in a hypothyroid child while on tab thyroxine. Scan shows
TcO4 thyroid scan in a hypothyroid child showing presence of native thyroid gland; (c)
Thyroid function can be evaluated by two methods:
1. Camera method: Using
99m
Tc04/
131
I or
123
I.
2. Uptake method: This is an invivo imaging method (radioactive count-based,
no image is produced); needs a special instrument called a thyroid uptake
probe. This procedure is popularly known as radioactive iodine uptake (RAIU).
16.2.2 Camera Method
16.2.2.1 Thyroid Imaging with
Technetium thyroid scintigraphy (
primary imaging for hyperthyroidism but a select Nuclear Medicine centers prefer
Radioiodine Uptake Studies (RAIU) before planning low dose
planning treatment for differentiated thyroid carcinoma
and 99Tc04 is not used to perform whole-body imaging in DTC.A
imaging does not accurately reect the disease burden.
Advantages of
99m
Tc04 imaging in hyperthyroidism:
99m
Tc04
99m
Tc04 thyroid imaging) is the widely chosen
131
131
I imaging is mandatory
I ablation. For
99m
Tc04 thyroid
16 The Role ofNuclear Medicine inThyroid andParathyroid Disorders
217
1. There is no specic preparation essential for the procedure.
2. The entire procedure is short and completed in about 30min.
3. There is no restriction to any age group, but it is avoided in pregnant and breast-
feeding ladies (relative contraindication).
4. The diagnosis is almost straightforward since characteristic thyroid uptake pat-
terns exist.
5. The procedure is cost-effective.
6. There are no signicant side effects.
When the imaging is planned for patients receiving antithyroid medications,
drugs are temporarily discontinued for 5–7 days for better imaging and to accurately estimate the thyroid gland's trapping function. Compared to
TcO4 imaging provides all the necessary information to plan low-dose
131
I imaging,
131
I therapy.
16.2.2.2 Procedure
The radiopharmaceutical is injected (2–4 millicurie (mCi) of
99m
Tc04) intravenously, and static images of the extended anterior neck are collected about (or
300–500kilo counts) about 15–20min later. An initial image is also acquired using
a Gamma camera to calculate the trapping function. Fast cine images (2s/frame for
1min) are used to study the characteristics of nodules when present.
99m
Tc04 accumulates in the thyroid gland because of the anionic transport mechanism and NIS
(sodium iodide symporter). Salivary glands and oral mucosa are also normally visualized. The evaluation of the nodules is precisely done with pinhole collimators,
which are expensive additional hardware that has to be attached to the gamma camera. Single-photon emission computed tomography (SPECT) is very helpful in
assessing nodules.
16.2.2.3 Interpretation
The features of a structurally and functionally normal thyroid has a characteristic
pattern and various pathological conditions thyroid alter these regular features that
are almost typical of that pathology [6]. The features regularly looked at in the scintigram include size, presence of a pyramidal lobe, percentage distribution of tracer
in each lobe, the total thyroid uptake, and the characteristics of nodules.
These abnormal tracer uptake patterns include diffuse or focal, homogeneous or
heterogeneous, increased or decreased when compared to parotid glands. The pyramidal lobe is identied as a tongue-shaped projection arising from one of the thyroid lobes or isthmus. Based on uptake by the nodule they are called as hot/cold.
Iodine uptake shall occur in outside the location of native thyroid in the esophagus,
ectopic thyroid sites like thyroglossal duct cyst, and substernal/retrosternal goiter.
Since the radiotracer is excreted in saliva and inadvertent swallowing can result in
extrathyroidal uptake in the esophagus. This is conrmed by a second image after a
gulp of water which washes off the activity. Thyroid scintigraphy conrms the
pathology of congenital hypothyroidism of neonates. Scintigraphy is useful inlocating functioning thyroid tissue in ectopic locations and perchlorate discharge test is
useful to identify peroxidase deciency conditions.