International Journal of Advancements in Research & Technology, Volume 2, Issue3, March-2013
ISSN 2278-7763
Functional Imaging In
Carcinoma Thyroid
PET has generated greatest interest with
perhaps the greatest utility being the
potential
Author Information:
1
localization
of
tumor
in
differentiated thyroid cancer(DTC) patients
1. Kamlesh Verma MS
Fellow, Surgical Oncology
TATA Memorial Centre
Mumbai, India.
E mail :
Kamleshverma2001@gmail.com
2. Sandeep Kumar MS , FRCS
Director , All India Institute Of
Medical Sciences , Bhopal , India.
E mail : k_sandeep@hotmail.com
3. Kaushal Yadav MS
Senior Resident, Surgical Oncology,
TATA Memorial Centre , Mumbai,
India.
E mail :
Kaushalyadavoo7@yahoo.com
Corresponding Author :
Kamlesh Verma MS
Fellow, Surgical Oncology
TATA Memorial Centre
Mumbai, India.
E mail :
Kamleshverma2001@gmail.com
who are radioiodine whole body scan
(WBS) negative and thyroglobulin (Tg)
positive. It is also useful in identification of
patients unlikely to benefit from additional
131I
therapy
and in
identification of
patients at highest risk of disease-specific
mortality,
which
may
prompt
more
aggressive therapy or enrollment in clinical
trials. Emerging data suggest that PET/CT
fusion studies provide increased accuracy
and modify the treatment plan in a
significant number of DTC cases whereas
studies
documenting
it’s
utility
in
Medullary&Anaplastic thyroid cancer are
scarce. Another potential utility of FDG-PET
is in guided surgery to assist in tumor
ABSTRACT:
localization in radio-iodine negative, FDG-
Thyroid imaging is a rapidly evolving field
PET
that has received numerous addendum. In
studies
current scenario thyroid imaging is not
survival and tumor recurrence attributable
limited to structural imaging but it has
to FDG-PET imaging in thyroid cancer
included
patients are lacking.Diffusion MRI is being
numerous
functional
imaging
positive DTC
patients.
documenting
improvements
studied
based imaging to PET and SPECT-CT. Of
potential
these functional imaging modalities FDG-
documenting the utility of SPECT-CT fusion
of
predicting
thyroid
the
in
modalities ranging from years old Iodine
Copyright © 2013 SciResPub.
in
Currently
malignant
nodules.Studies
International Journal of Advancements in Research & Technology, Volume 2, Issue3, March-2013
ISSN 2278-7763
2
imaging are limited to identification of
more
residual
recurrent/residual thyroid carcinoma.
foci
in
neck
and
systemic
accurate
evaluation
metastasis. This article reviews the utility
Imaging
and
imaging
patients with thyroid cancer may be
modalities in thyroid cancer management,
subdivided into structural and functional
and offers practical recommendations
imaging
limitations
of
functional
technologies
categories.
used
Structural
to
of
assess
imaging
entails the assessment of morphologic
features of thyroid malignancy and that of
1. INTRODUCTION:
adjacent structures within which it is
Thyroid cancer is most common endocrine
confined. Functional imaging is comprised
malignancy, accounting for 94.6% of the
of a multitude of noninvasive imaging
total new endocrine cancers, and 66.0% of
techniques that are currently in use to probe
the deaths due to endocrine cancers. The
tumor molecular processes, and to study
discrepancy between the total number of
tumor physiology, in vitro and in vivo.
cases of all endocrine cancers arising in the
Functional imaging can be implemented
thyroid (94.6%) and the total proportion of
through use of diffusion-weighted imaging
endocrine cancer deaths (66.0%) reflects the
(DWI),
relatively indolent nature and long-term
magnetic resonance imaging (DCE-MRI),
survival
magnetic resonance spectroscopy (MRS) as
associated
with
thyroid
dynamic
contrast-enhanced
malignancies.
well
In recent years thyroid imaging has made
tomography
exponential
emission computed tomography(SPECT).
changing
treatment,
progress,
the
considerably
approach
prognosis,
to
diagnosis,
follow-up
and
as
through
(PET)
positron
and
emission
single-photon
2. RATIONALE FOR FUNCTIONAL
IMAGING:
evaluation of thyroid cancer. Moreover this
notable technical advance has proven its
Cross-sectional structural imaging by CT,
ability
MRI, and US is currently used in standard
for
identification
of
incidental
thyroid nodules and the achievement of
clinicalpractice
on
a
daily
basis
to
qualitatively or semi quantitatively detect,
Copyright © 2013 SciResPub.
International Journal of Advancements in Research & Technology, Volume 2, Issue3, March-2013
ISSN 2278-7763
3
characterize, stage,assess posttherapeutic
molecular
response, and determine recurrence of
processes and physiology of tumors are
malignant
notobtained. As such, structural imaging at
tumors.
Theseimaging
techniques are based on structural features
a
such
adequate
as
tumor
shape,
size,
margins,
characteristics,
singletime
point
may
biological
not
provide
informationregarding
patient
location, spatial extent, attenuation (on CT),
prognosis, probabilityof tumor response to
signal intensity (on MRI), echogenicity (on
therapeutic
US), or gross degree of enhancement
development.
afterintravenous contrast administration.
2.1 Radio-iodine and Non radio-iodine
Despite its many contributions to the
based Thyroid Scintigraphy:
management
of
patients
with
cancer,
structural imaging alone suffers from many
shortcomings in such settings.
tissue at the molecular, sub-cellular, or
cellular levels proceed in time to gross
macroscopic changes in tissues or organs
to
cancer
[1],
[2].This
has
significantimplications with regard to early
detectionof cancer for screening purposes,
as well as formonitoring response to
therapeutic intervention. The second is that
macroscopic
abnormalitiesare
often
nonspecific and often seenin nonneoplastic
conditions. For example,enlarged lymph
nodes in the setting of known malignancy
may be either be due to metastaticdisease or
due to reactive hyperplasia in inflammatory
disease [3]. The third is thatdata regarding
Copyright © 2013 SciResPub.
new
drug
It is a planar imaging technique using
gamma
camera
using
radiopharmaceuticals,
The first is that alteration in tumor
due
intervention,and
99mTcO4,
most
various
commonly
Iodine-123-iodide
(123I)
and
Iodine-131-iodide (131I). Use of 123-I and
131-I is more physiological as Iodine is
trapped
and
metabolized
by
thyroid
follicular cells whereas 99mTcO4 undergoes
no further alteration in thyroid cells.
Routine use of 131-I and 123-I
in clinical
thyroid
somewhat
unpractical
scintigraphy
due
to
is
their
logistic
and
physical limitations. 123I is a cyclotron
product and therefore not universally
available and relatively expensive moreover
it has pure gamma emission of 159 KeV and
is ideal for in vivo gamma camera imaging
with a reasonable half-life of 13 hours.
International Journal of Advancements in Research & Technology, Volume 2, Issue3, March-2013
ISSN 2278-7763
4
Radioiodine 131-I has been superseded by
encountering electrons, lead to emission of 2
99mTcO4 for thyroid imaging due to its
gamma rays directed at 180 degrees from
higher gamma emission of 364 KeV and
each other. Sites of tracer accumulation in
long half-life of 8 days leading to noisy
the body are thus determined by detection
images and un-necessary high radiation
of these paired gamma rays, which is
burden. In addition to its therapeutic
termed
function that stems from its beta emissions,
detection.”Currently,whole-body
it has retained its imaging function in post-
has been approved foruse in assessing
surgical follow-up of differentiated thyroid
suspected recurrenceof well-differentiated
carcinoma.
thyroid cancer(WDTC) in patients with
Other radiopharmaceuticals, with different
mechanism of uptake, include 201Tl or
“coincidence
radioiodinenegativescans
and
PET-CT
detectable
thyroglobulin(Tg) levels.
99mTc-MIBI [4], [5] which is used in the
FDG-PET
assessment of cold nodules and post-
Incidentalomas:Thyroid incidentaloma is
surgical follow-up especially in noniodine
defined as a newly identified thyroid lesion
avid thyroid carcinoma.
encountered during an imaging study for
2.2 Positron Emission Tomography Scan:
in
non-thyroidal
the
disease
Assessment
.
Due
to
of
the
increasingly extensive use of ultrasound
PET and now PET/CT are recent addition in
(US), computed tomography (CT), magnetic
thyroid cancer imaging armamentarium.
resonance (MR) and 18F-FDG PET imaging,
The concept of fusion of anatomic and
an incidental finding of a nonpalpable
metabolic imaging as “anatometabolic”
thyroid nodule is a common problem.
images has been present for nearly 15 years,
Structural
but has been transformed into a valuable
accurately differentiate between benign and
clinical practice only quite recently. PET is a
malignant thyroid nodules. Most centers
type of emission computed tomography
use fine needle-aspiration (FNA) cytology
that is used to study the distribution of
for this purpose. However, FNA has several
radiolabeled tracers within the body. PET
shortcomings, such as its inability to
radiotracers emit positrons
Copyright © 2013 SciResPub.
that,
after
imaging
techniques
cannot
International Journal of Advancements in Research & Technology, Volume 2, Issue3, March-2013
ISSN 2278-7763
5
provide a diagnosis due to sampling error
follow up enabling correct diagnosis. A
or its inability to clearly differentiate benign
benign etiology was determined in 31/48
follicular adenomas from welldifferentiated
(64.6%), while 17/48 patients (35.4%) had
follicularcarcinomas [6]. The ability to better
malignancy confirmed or had FNA highly
distinguish
suspicious of malignancy, with papillary
benign
from
incidentalomascould
be
functional
and
imaging
patients
undergoing
malignant
achieved
with
carcinoma confirmed in 12/17 of those
might
spare
malignancies. Median SUVmax for the
unnecessary
benign group was 5.6, range 2.5-53.Median
investigations and surgical resection.
SUVmax for the malignant lesions was 6.4,
The normal thyroid gland shows low grade
range 3.5-16. SUVmax between benign and
FDG uptake or is usually not visualized on
malignant groups was not statistically
the whole-body 18F-FDG PET scan [7], [8].
different (p=0.12). There have been other
Diffuse increased thyroid FDG uptake is
retrospective studies using 18F-FDG PET.
usually an indicator of chronic thyroiditis
In patients who had adequate follow-up,
[9] but has also been described in Grave’s
Cohen et al. (12), Kang et al. (13) and Kim et
disease [10]. Several retrospective studies
al. (14) found malignancy in 47% (7/15), 27%
have assessed the incidence and causes of
(4/15) and 50% (16/32), respectively.
focal increased uptake within the thyroid
gland
on
18F-FDG
PET.
There
Despite
the
non-discriminatory
value of SUV mentioned
earlier, a
isdisagreement on standard uptake value
significant number of studies have found it
(SUV) which can differentiate between
to be useful in differentiating benign from
benign and malignant thyroid nodules. A
malignant focal thyroid lesions. Bloom et al.
retrospective
study
al
[15] looked at 12 patients with focal thyroid
[11]reviewed
18F-FDG
scans
uptake. Four malignant lesions (3 papillary
by
Bogsrudet
PET-CT
performed over a three-year period
and
and
1
follicular
8
benign
all
had
measured the maximum SUV (SUVmax) of
SUVmax>8.5.
thyroid incidentalomas. They found focal
(follicular adenomas) had SUVmax<7.6.
incidental high uptake in79/7,347 patients
Supportive data comes from Cohen et al.
(1.1%). Of these, 48 patients had adequate
[12] who found that seven patients with
Copyright © 2013 SciResPub.
The
carcinoma)
lesions
International Journal of Advancements in Research & Technology, Volume 2, Issue3, March-2013
ISSN 2278-7763
6
malignant thyroid lesions had significantly
correlate
higher SUV on average (6.92±1.54, range
levels,[23] suggesting that small lesion
4.1-14.5), compared with seven patients
volume may be a cause of false-negative
with benign lesions(3.37±0.21, range 2.9-4.9).
studies.
PET Scan in followupof
Role of rhTSH in FDG PET-CT:Several
scan
is mainly used in detection of
recurrentdisease
in
negativeradioiodine
are
WDTC:PET-CT
patients
However,if
to
the
with
glucose transporters
thyroglobulin
(Glut) have been
with
described that move glucose into cells.
scans.[16-21]WDTCs
Glut1 is expressed in aggressive thyroid
generallyslow-growing
somecapacity
positively
and
concentrate
cancer
retain
iodine.
carcinomas.
TSH
stimulation
increases
glucose metabolism in thyroid cells, and
becomes
more
increases
gradually
loses
Triiodothyronine and Levothyroxine may
decreased
increase both Glut1 and Glut4 expression.
sodium-iodine
These findings suggest that recombinant
symportersand becomes undetectable by
human TSH (rhTSH) may offer the unique
the radioiodine scan. By virtue of their
opportunity to take advantage of both
increased growth rate and subsequent
mechanisms
increased
thyroid
poorlydifferentiated,
it
thiscapacity—mainly
due
expression
of
to
the
utilization
of
glucose,
these
Glut
by
1
expression.
continuing
replacement/
exogenous
suppression
and
lesions then become detectable by FDG
simultaneously providing TSH stimulation.
PET-CT imaging . The radioiodine and the
Petrich et al. [24] investigated 30 patients
PET-CT
with FDG-PET during TSH suppression and
scans
are,
therefore,
complementary in this clinical scenario. [19]
again
In a meta-analysis of 17 studies comprising
suppression, PET scans were positive in
571 patients, the pooled sensitivity and
30% with identification of 22 tumor-like
specificity of FDG PET-CT in patientswith
foci. After rhTSH, 63% had positive PET
recurrent cancer but negative radioiodine
scans with 78 tumors-like foci identified (15
scanswere shown to be 0.835 and 0.843,
of
respectively [22].
Detection of recurrence
confirmed as tumor). Although it is logical
on the PET-CT scan has been shown to
to accept that rhTSH can be used to
Copyright © 2013 SciResPub.
after
these
78
rhTSH.
foci
were
During
TSH
subsequently
International Journal of Advancements in Research & Technology, Volume 2, Issue3, March-2013
ISSN 2278-7763
7
improve the sensitivity of FDG PET-CT for
negative or inconclusive in the presence of
thyroid malignancy, more data are needed
raised tumor markers such as calcitonin and
to determine the true usefulness of rhTSHin
carcinoembryonic antigen (CEA). Some
this indication.
studies show that FDG PET-CT is superior
Iodine-124 as a PET radiopharmaceutical :
to
Because of the spatial resolution limitations
ultrasound, contrast enhanced CT, and
of 123I or 131I and the widespread
111In octreotide scans in the detection of
availability of PETCT imaging, interest is
recurrent
growing in using 124I and PET to image
diagnostic accuracy of FDG PET-CT for
thyroid malignancies. 124I, a positron-
MTC is limited compared with its use in
emitting isotope with a half-life of 4.2 days,
WDTC.
combines the resolution and localization
reported
advantages of PET-CT with the specificity
80%;[31] however, detection rates seem to
of an iodine-based tracer in imaging the
improve
thyroid.
higherserumcalcitonin levels.
Freudenberg et al[25]compared 124I
conventional
modalities,
MTC.[28,29]
Overall
to
as
However,
sensitivity
range from
in
such
has
the
been
47.4%[30]
patients
18F-dihydroxyphenylalanine(18F
to
with
DOPA)
PET-CT with FDG PET-CT in patients with
and 68Ga-DOTA peptides that bind to
elevated
negative
somatostatin receptors, such asDOTA-TOC
ultrasonography and found the sensitivities
and DOTA-NOC, are also being evaluated
forWDTC detection to be 80% and 70%,
for this indication.
respectively. Other recent articles have also
Anaplastic thyroid cancer: Due to its
pointed out therole of 124I in recurrence
aggressive
detection, as well as in quantifying patient-
significantly
specific radioiodine therapydosimetry prior
FDG PET-CT can be utilized to detectboth
to ablation [26], [27].
primary and metastatic anaplasticthyroid
Medullary thyroid cancer:Currently, FDG
cancer.
PET-CT in medullary thyroid cancer is most
foundthat
commonly
FDGdetectedall
thyroglobulin
conventional
used
in
imaging
Copyright © 2013 SciResPub.
but
cases
modalities
where
are
growth
andsubsequent
elevated
glucoseutilization,
Astudy
by
Nguyenet
PET-CT
primary
al[32]
imagingwith
tumor
and
nodalmetastases,as well as 5 out of 8 lung
International Journal of Advancements in Research & Technology, Volume 2, Issue3, March-2013
ISSN 2278-7763
metastases.However,
for
better
Pitfalls of
8
PET Imaging:One intrinsic
characterization of FDGPET-CT’s diagnostic
limitation of PET derives from the nature of
accuracy,morestudies are needed.
positron
Impact of FDG-PET Imaging on outcome
coincidence detection. A positron generally
of
must travel a certain distance in tissues
Thyroid
Cancer
Patient:Studies
decay
and
on patient survival are lacking. Initial
Annihilation occurs approximately 1 to 2
studiesin small series of patients showed
mm away from the positron’s origin. This
PET/CT to be superior to either PET or CT
phenomenon places a theoretical limit on
alone for approximately 25% of patients by
PET’s achievable spatial resolution, which is
identifying recurrent tumors or metastatic
estimated at 2 to 3 mm. False-negative
lymphadenopathy
results
[33].
are
an
of
before
surgery
with
principle
documenting impact of FDG-PET imaging
before
colliding
the
encountered
in
well-
and a specificity and a positive predictive
differentiated lesions. False-positive results
value of 100% for the diagnosis of recurrent
are due to uptake in normal brown fat and
thyroid cancer.Despite a lower negative
inflammatory lesions but these can easily be
predictive
provided
ruled out through careful review of the
unknown
clinical history and other imaging.It has
additional,
previously
information
that
altered
further
been
noted
that
sites
or
very
smalllesions
PET/CT
mm)
with
PET/CT had a reported sensitivity of 66%
value,
(<4
electron.
of
metastasis
management in 40% of patients [34]. An-
visualized better with 18F-FDG include
other study reported similar results for
cervical and mediastinal lymph nodes,
patients with iodine-negative suspected
whereas lung and bone lesions showed less
recurrence of thyroid cancer, with an
uptake compared to 131I scan and 99mTc-
improved diagnostic accuracy of PET/CT of
MIBI .
93%, compared with an accuracy of PET of
2.3
78%. In addition, fused images led to a
Imaging :
change
in
management
patients[35].
in
48%
of
Functional
Magnetic
Resonance
The role of MRI in the evaluation of
thyroid lesions has become more important
in recent years because of the development
Copyright © 2013 SciResPub.
International Journal of Advancements in Research & Technology, Volume 2, Issue3, March-2013
ISSN 2278-7763
of surface coils and functional MRI such as
SPECT
9
involves
the
use
of
perfusion imaging and Diffusion Weighted
radioisotopes that emit single gamma rays
MR imaging (DWI). DWI is a non-invasive
in arbitrary directions, thus requiring the
diagnostic method which evaluates the
presence
mobility of water in different tissues to
determine sites of tracer accumulation in
generate diffusion weighted images and
the body. While the collimators provide
Apparent
directionality, they screen out most of the
Diffusion
Coefficient
(ADC)
of
a
metallic
collimator
to
maps.
emitted photons. SPECT/CT is new addition
Schueller et al [36] performed a prospective
in thyroid imaging. Most of the literature
study on 31 patients during 18 months
showing utility of SPECT/CT in thyroid
period ,
were posted for total
imaging is limited to single institution case
thyroidectomy . MRI including DWI was
series. In a study by Angela Spanu et al.[37]
performed day before surgery.Six patients
based on 117 consecutive thyroidectomized
were excluded from the study due to
DTC
motion artifacts and poor image quality in 3
with traditional planar imaging technique ,
patients and a solitary nodule with a size <8
131I scintigraphy. Planar 131I imaging
mm in 3 patients. At surgery, 5 patients had
showed 116 foci of uptake in 52 of 117
adenoma,
papillary
patients. SPECT/CT showed 158 foci in 59 of
thyroid carcinoma (PTC), 6 had medullary
117 patients, confirming all 116foci seen on
thyroid
planar imaging in 52 of the patients. In the
who
10
had
carcinoma
(MTC),
and 4
had
patients SPECT/CT was compared
follicular thyroid carcinoma (FTC).The ADC
neck,
values
showed 67and 81 foci, respectively. Outside
for
thyroid
significantly from
and
SPECT/CT
of
the neck, planar imaging showed 49 foci in
There were
no
16 patients and SPECT/CT showed 77 foci
significant differences between the ADC
in 18 patients.In this study both SPECT/CT
values for the 3 types of carcinoma (P > .05).
and planar imaging were concordantly
2.4 131I-Iodide SPECT/CT:
negative in 49.6% and concordantly positive
(P =
ADC
differed
imaging
values
adenomas
the
cancer
planar
.004) .
in 44.4% and discordant (planar imaging
negative and SPECT/CT positive) in 6%. In
Copyright © 2013 SciResPub.
International Journal of Advancements in Research & Technology, Volume 2, Issue3, March-2013
ISSN 2278-7763
10
35.6% of patients with positive findings,
above conclusion should be based on large-
more
scale
appropriate
decision
about
multi-centre
prospective
stratification
of
studies
therapeutic management was made. All
enabling
lesions determined to be a presumptive
statistically
tumor on SPECT/CT were confirmed to be
subgroups.
malignant.
2.5. FDG RADIO-GUIDED SURGERY:
meaningful
patients
into
homogeneous
Kraeber-Bodere et al. have reported FDG
In another study by Ka Kit Wong et al[38]
SPECT/CT was used for post thyroidectomy
staging before giving ablative dose of 131I
in forty-eight patients.SPECT/CT changed
the planar scan interpretation for 19 (40%)
of 48 patients, detecting regional nodal
metastases in four patients and clarifying
equivocal focal neck uptake in 15 patients.
Daniela Schmidt et al[39] studied the
diagnostic value of 131I SPECT/CT
on
nodal staging of fifty seven patients with
radio-guided surgery to assist in tumor
localization in radio-iodine negative, FDGPET positive DTC patients [40]. All FDGPET
visually
identified
lesions
were
detected with the gamma probe, and the
mean tumor activity was 40% higher than
the surrounding neck tissue. Additional
studies will be necessary to clarify the
ability of radio-guided surgery to render
patients free of disease, or reduce local
tumor recurrence.
thyroid carcinoma at the first ablative
radioiodine therapy.SPECT/CT led to a
revision of the original diagnosis in28 of 143
cervical foci of radioiodine uptake seen on
planar imaging.
improvements brought about by SPECT/CT
in patients with thyroid carcinoma are
considerable. However, considering the
clinical
Imaging remains an integral tool for clinical
detection,staging,
thyroid
These pilot studies suggest that diagnostic
variable
3. CONCLUSIONS:
presentations
of
differentiated thyroid cancer, validity of the
Copyright © 2013 SciResPub.
and
cancer.
significantimprovements
resolution
management
havebeen
of
While
in
anatomic
achieved,
(131)I
thyroid scan continues toyield significant
numbers
of
false
negativestudies.
Furthermore, traditional anatomic thyroid
cancerimaging (ie, size and morphology)
International Journal of Advancements in Research & Technology, Volume 2, Issue3, March-2013
ISSN 2278-7763
11
provides limited information about the
underlying tumor biology. A clear challenge
4. REFERENCES:
for
to
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