1) Fifteen patients with differentiated thyroid cancer underwent 124I positron emission tomography/computed tomography (PET/CT) imaging to determine the extent of disease and evaluate radioactive iodine kinetics. 2) 124I PET/CT identified 46 distinct lesions in the 15 patients with a sensitivity of 92.5%, detecting 22.5% more lesions than subsequent 131I scans. 3) The study demonstrated different kinetic profiles for normal thyroid remnants, salivary glands, and metastatic lesions, as well as variations in functional volumes and cumulated activity among lesions.

1. THYROID RADIOLOGY AND NUCLEAR MEDICINE
124
I PET/CT in Patients with Differentiated Thyroid Cancer:
Clinical and Quantitative Image Analysis
Seza A. Gulec,1
Russ A. Kuker,2,3
Mohammed Goryawala,2
Carlos Fernandez,4
Rudolfo Perez,5
Alina Khan-Ghany,6
Ana Apaza,6
Evis Harja,6
and Mack Harrell7
Background: Although radioactive iodine (RAI) imaging/therapy is one of the earliest applications of ther-
anostics, there remain a number of unresolved clinical questions as to the optimization of diagnostic techniques/
protocols and improvements in patient-specific treatment planning strategies. The objectives of this study were
to determine the imaging characteristics and clinical feasibility of 124
I positron emission tomography/computed
tomography (PET/CT) for the determination of extent of disease and evaluation of RAI kinetics in its physi-
ologic and neoplastic distribution in patients with differentiated thyroid cancer (DTC).
Methods: The study was designed as a prospective phase II diagnostic trial of patients with confirmed DTC.
Following adequate preparation, patients received 2 mCi 124
I in liquid form and sequential whole-body PET/CT
imaging was performed at five time points (2–4 h, 24 – 6 h, 48 – 6 h, 72 – 6 h, and 96 – 6 h post-administration).
All patients who had 124
I imaging subsequently underwent RAI treatment with 131
I, with administered activities
ranging from 100 to 300 mCi. Post-treatment scans were obtained 5–7 days after RAI treatment. A by-patient
and by-lesion analysis of the 124
I images was performed and compared with the post-treatment 131
I scans as well
as F-18 FDG PET/CT images. Quantitative image analysis was also performed to determine the total functional
volume (mL), activity per functional volume (lCi/mL), and cumulated activity (lCi/h) for remnants, salivary
glands, and nodal metastases.
Results: Fifteen patients (6 women; Mage = 57 years; range 29–91 years) were enrolled into the study. Forty-six
distinct lesions were identified in these 15 patients on 124
I PET/CT images, with a sensitivity of 92.5%. In
addition, 124
I identified 22.5% more foci of RAI-avid lesions compared with the planar 131
I post-treatment scans.
This study demonstrates different kinetic profiles for normal thyroid remnants (peaked at 24 h with mono-
exponential clearance), salivary glands (peaked at 4 h with bi-exponential clearance), and metastatic lesions
(protracted retention), as well as individual variations in functional volumes and thus cumulated activities.
Conclusions: 124
I PET/CT is a valuable clinical imaging tool/agent, both in determining the extent of disease in
the setting of metastatic DTC and in the functional volumetric and kinetic evaluation of target lesions.
Introduction
Although radioactive iodine (RAI) imaging/therapy
is one of the earliest applications of theranostics, there
remain a number of unresolved clinical questions as to the
optimization of diagnostic techniques/protocols as well as
improvements in patient-specific treatment planning strate-
gies (1–9). Current clinical RAI imaging is performed by
using either 131
I or 123
I. 131
I has a half-life of 8.02 days and
has beta (Emax = 606 keV) and gamma (364keV) emissions.
The administered activity is usually 2–5 mCi. The clinical
safety/efficacy of higher administered activities has been
questioned due to the concern for stunning when it is used just
before RAI treatment (10–12). Although the half-life is suit-
able for sequential (time course) imaging, the image quality is
less than optimal for accurate extent of disease (EOD) evalu-
ation and quantitation. 123
I has gamma (159keV) emissions
only. This energy profile is better suited for standard gamma
1
Department of Surgical Oncology, Endocrine Surgery, Florida International University Herbert Wertheim College of Medicine, Miami, Florida.
Department of 2
Radiology; 3
Division of Nuclear Medicine; University of Miami Miller School of Medicine, Miami, Florida.
4
Department of Radiology, Elite Imaging Center, Miami, Florida.
5
Department of Endocrinology, Thyroid Medical Institute, Miami, Florida.
6
Department of Endocrinology, Chen Medical Associates, Miami, Florida.
7
Department of Endocrinology, Memorial Health Care System, Hollywood, Florida.
THYROID
Volume 26, Number 3, 2016
ª Mary Ann Liebert, Inc.
DOI: 10.1089/thy.2015.0482
441

2. camera imaging, and higher activities can be used with much
less concern for stunning. However, the 13-hour half-life does
not allow sequential imaging over a period of several days. 124
I
sodium iodide (124
I) is a positron emission tomography (PET)
radiopharmaceutical with a 4.2-day half-life. It potentially
offers better imaging characteristics and has a favorable half-
life that permits the evaluation of in vivo iodine kinetics. It has
a rather complex decay schema, which creates challenges in
optimal imaging (13). There exist a number of reports attesting
the potential clinical benefits of 124
I imaging in patients with
differentiated thyroid cancer (DTC). However, a uniform
clinical protocol for imaging, image analysis, and quantitation
has not been firmly established (14–22).
Study Design
The study was designed as a prospective phase II diagnostic
trial with the objectives to determine the imaging character-
istics and clinical feasibility of 124
I PET/computed tomogra-
phy (CT) imaging for determination of extent of disease and
evaluation of RAI kinetics in its physiologic and neoplastic
distribution in patients with DTC. Patients with confirmed
differentiated (both well-differentiated and poorly differ-
entiated) thyroid cancers were studied. Patients who were
newly diagnosed, as well as those who had known or suspected
recurrent/metastatic disease, were eligible for the trial. The
inclusion criteria for the study included a histological con-
firmation of DTC and a clinical indication for RAI imaging
(detection of known or suspected postoperative residual
thyroid bed or nodal disease, extent-of-disease evaluation in
known recurrent/metastatic disease, suspicious nodule/mass
detected by physical exam, imaging study or fine-needle
aspiration, recurrent/metastatic disease suspected by ele-
vated thyroglobulin), age ‡18 years, ability and willingness
to give written consent, life expectancy >3 months, and Kar-
nofsky performance status ‡70. Pregnant and nursing women
and individuals allergic to iodine were excluded from the
study. The study was approved by the Institutional Review
Board, and was conducted in accordance with institutional
investigational new drug (IND)/research guidelines.
Material and Methods
124
I sodium iodide
The 124
I sodium iodide utilized for this study was obtained
from IBA Molecular N.A., Inc. It was provided in a 0.02 N
aqueous NaOH solution with a radiochemical purity (RCP)
>95% iodide, radiochemical impurity <5% (iodate and
diiodate), and a radionuclide purity (RNP) >99.9% at cali-
bration. The chemical purity was determined with Tellurium
(Te) <1 lg/mL. The RCP and RNP stabilities were verified
for 10 days.
124
I imaging protocol
The administered activity for 124
I was 2 mCi by oral ad-
ministration in liquid form. The basic imaging protocol in-
volved a five time-point (2–4 h, 24 – 6 h, 48 – 6 h, 72 – 6 h,
and 96 – 6 h post-administration) whole-body PET/CT im-
aging schedule. The patients were prepared for RAI imaging/
dosimetry either by withholding suppressive thyroxine for an
adequate length of time (to achieve a thyrotropin [TSH] level
of >50 at the time of imaging) or by administering recom-
binant human TSH (rhTSH; two consecutive daily doses of
0.9 mg intramuscularly, in the days preceding RAI adminis-
tration). Two patients in the study cohort were prepared using
the rhTSH protocol. These patients underwent 124I imaging
after receiving the standard two-day rhTSH injections. They
received a second set of rhTSH injections for the 131
I treat-
ment. The remaining patients were prepared using the with-
drawal protocol. PET/CT scans were performed on a Siemens
Biograph TruepointÔ scanner and combined with low-dose
CT for attenuation correction and anatomic localization.
Scans were obtained from the top of the head to the feet. An
acquisition time of 5 min per bed position was used, with it-
erative 3D reconstruction by four iterations with eight subsets
and a Gaussian filter.
131
I imaging protocol
All patients who had 124
I imaging subsequently underwent
RAI treatment with 131
I sodium iodide, with administered
activities in the range 100–300 mCi. Post-treatment scans
were obtained 5–7 days after RAI treatment. Anterior and
posterior planar whole-body scans, as well as static antero-
posterior and oblique neck images, were acquired.
Image analysis
The localization of 124
I in known/suspected lesions, includ-
ing cervical and remote metastatic sites, was documented. 124
I
images were compared to post-treatment 131
I images. Com-
parisons were performed on a by-patient and by-lesion basis.
All images were reviewed and analyzed by two experienced
nuclear medicine physicians. Quantitative image analysis
was performed using semiautomatic region of interest (ROI)
methodology. The total functional volume (mL), activity per
functional volume (lCi/mL), and cumulated activity (lCi/h)
for remnants, salivary glands, and nodal metastases were cal-
culated. The 124
I images were also compared to F-18 FDG
PET/CT images that were acquired prior to RAI treatment in
all patients. F-18 FDG PET/CT imaging was performed as part
of a comprehensive extent of disease evaluation and not for the
purpose of this study per se.
Relative sensitivity determination for 124
I PET/CT
versus post-treatment planar 131
I imaging
Comparative image analysis was performed on a by-patient
and by-lesion basis. For the purposes of by lesion analysis, any
distinct uptake noted on 124
I PET/CT or post-treatment 131
I
planar images was considered ‘‘positive reference.’’ A posi-
tive reference implies presence of a tumor/remnant with RAI
uptake. The true positive (TP) and false negative (FN) des-
ignations, and the sensitivity calculations for 124
I and 131
I
imaging were performed based on the ‘‘positive reference.’’
The sites of physiologic uptake were carefully identified. A
physiologic uptake was not considered as false positive (FP).
A true negative (TN) designation was used when both 124
I and
131
I images were negative. The complete chart for TP, TN, FP,
and FN designations are explained in Table 1.
Results
Fifteen patients (6 women; Mage = 57 years; range 29–91
years) were enrolled into the study. All patients underwent
2 mCi diagnostic 124
I imaging. All but one patient completed
442 GULEC ET AL.

3. all 5 days of data collection for dosimetry; one patient only
completed 2 days of data collection due to personal reasons.
Forty-six distinct lesions were identified in 15 patients (11
remnant tissue, 19 metastatic neck nodes, 3 residual neck
tumors, 5 metastatic mediastinal/hilar nodes, 5 metastatic
lung disease [diffuse micro- or macronodular uptake], and 3
metastatic abdominal tumors). The 46 distinct lesions are the
aggregate sum of all the imaging modalities. This number
also includes the lesions identified on FDG PET/CT. By
virtue of image detail on 124
I images, the thyroid remnant was
further divided into ROIs, including the right and left remnant
lobes as well as the pyramidal lobe. These were not sepa-
rately identified on the post-treatment 131
I scans. FDG PET/
CT was clinically indicated and performed in all 15 patients.
Therefore, 124
I PET/CT to FDG PET/CT image comparison
was possible in all patients. The FDG(+)/RAI(–) lesions were
considered to be functionally dedifferentiated, and were thus
stratified as a different biological group, and not considered
FN. All patients received therapeutic 131
I, with administered
activities ranging from 100 to 300 mCi, and underwent post-
treatment imaging.
Remnant uptake and kinetics
There were eight patients with thyroid remnants, status post
recent total thyroidectomy (RAI-naive). By-patient analysis
indicated that remnant uptake was demonstrated in all of these
patients on both 124
I and 131
I imaging studies. A total of 11
Table 1. Diagnostic Utility Profile for RAI Imaging, and the TP, TN, FP, and FN
Designations Based on Disease Detection Profile and Image Characteristics
Image characteristics
Disease detection profile 124
I 131
I
124
I (+) 131
I (+) FDG (–) Tg (–) TP TP
124
I (+) 131
I (-) FDG (–) Tg (–) TP FN
124
I (-) 131
I (+) FDG (–) Tg (–) FN TP
124
I (-) 131
I (-) FDG (-) Tg (-) TN
NED
124
I (-) 131
I (-) FDG (+) Tg (–) TN
iodine-refractory measurable disease
124
I (-) 131
I (-) FDG (-) Tg (+) TN
iodine-refractory unmeasurable disease
TP, true positive; TN, true negative; FP, false positive; FN, false negative; NED, no evidence of
disease; RAI, radioactive iodine; Tg, thyroglobulin.
FIG. 1. The uptake and clearance pattern in thyroid remnants. The time–activity curve shows a peak at 24 hours followed
by exponential decay.
124
I PET/CT IN THYROID CANCER 443

4. distinct foci of remnant uptake were identified. 124
I dis-
tinctly defined remnant uptake in right lobe, left lobe, and
isthmus/pyramidal lobe anatomic sites. 124
I was positive in
11/11 (100%). 131
I revealed 9/11 (82%) distinct remnant
foci. The two missed foci of remnant uptake by 131
I were in
the trajectory of the pyramidal lobe in the midline. FDG was
negative in all remnant tissue, and none of the thyroid
remnants was visually detected as a soft-tissue abnormality
on CT. The sequential 124
I images consistently demon-
strated the maximum remnant activity to occur at 24 h. After
the peak activity was reached, the clearance was mono-
exponential, as shown in Figure 1. The maximum remnant
activity ranged from 1.2 to 215.9 lCi, with the total func-
tional remnant volume (the total number of voxels within
the remnant ROI) ranging from 1 to 60 mL. The activity per
volume of remnant tissue ranged from 0.036 to 11.265 lCi/
mL. The total cumulated activity within the remnant ranged
from 68 to 12757.3 lCi/h.
Salivary gland uptake and kinetics
Physiologic salivary gland activity was demonstrated in all
15 patients, with the activity reaching a peak at 4 h after
radioiodine administration. The salivary gland clearance was
bi-exponential, with an average of 81% of the activity being
cleared from the salivary glands by 24 h.
Nodal disease uptake and kinetics
There were 19 distinct foci of uptake identified as nodal
metastasis. 124
I was positive in 16/19 (84%). 131
I revealed 9/19
(47%) distinct foci of nodal uptake. The three negative nodes
by 124
I were also negative by 131
I but positive on FDG (iodine-
refractory nodal disease). Nodal metastatic disease demon-
strated a pattern of uptake that was significantly different from
the thyroid remnant or physiologic salivary gland activity. A
protracted retention was identified as a characteristic pattern
for metastatic nodal disease, as shown in Figure 2.
Lung disease
There were five cases of metastatic lung disease (2 micro-
nodular, 3 macronodular). One case was negative on both 124
I
and 131
I, but was positive on FDG (iodine-refractory disease).
Of the remaining four cases with metastatic lung disease, 124
I
was positive in 1/2 cases with macronodular disease, but was
negative in 2/2 cases with micronodular metastatic disease.
131
I post-treatment scans were positive in 4/4 cases. The case
of macronodular disease that was negative on 124
I and positive
on 131
I was also positive on FDG and may be in the process of
undergoing dedifferentiation.
Abdominal disease
There was only one patient with abdominal disease. This
was a very unusual case that presented with metastatic ab-
dominal disease, and no primary was identified in the total
thyroidectomy specimen. The disease was discovered at ex-
ploratory laparotomy and confirmed by hematoxylin and
eosin and immunohistochemistry (for thyroglobulin and
TTF-1 staining). A subsequent FDG study showed hepatic,
mesenteric nodal, and peritoneal disease. 124
I demonstrated
positive uptake in all abdominal lesions. However, 131
I was
only positive in the hepatic disease.
FIG. 2. The uptake and clearance pattern in lymph node metastasis. The time–activity curve demonstrates a slow upslope
to the peak activity with a protracted retention.
444 GULEC ET AL.

5. The comparative uptake patterns of 124
I and 131
I and the
overall sensitivity for respective imaging modalities are
presented in Tables 2 and 3.
Discussion
This prospective phase II study demonstrates that 124
I PET/
CT imaging is clinically feasible, has high lesion detection
sensitivity, and offers an additional advantage of quantitation,
which can readily be translated into high-quality dosimetric
input (activity determination for absorbed dose calculations).
This study is unique in that it utilizes post-treatment 131
I im-
aging as the gold standard as opposed to routine diagnos-
tic activities of 131
I, which have known limitations in lesion
detection.
Van Nostrand et al. compared the ability of diagnostic 124
I
PET/CT images (1.7mCi) with 131
I planar whole-body imag-
ing (1–2mCi) in detecting residual thyroid tissue and/or met-
astatic well-differentiated thyroid cancer. Their data concluded
that relative to 131
I planar whole-body imaging, 124
I PET/CT
identified as many as 50% more foci of radioiodine uptake in as
many as 32% more patients (23). The present study not only
indicates an improved benefit in lesion detectability with 124
I
PET/CT, but also demonstrates its by lesion detection power
(sensitivity) when matched against the gold standard of iodine-
avid disease, which is a post-treatment 131
I scan after thera-
peutic doses ranging from 100 to 300mCi. When using 131
I
post-treatment scans as the gold standard, 124
I PET/CT iden-
tified 22.5% more foci of RAI-avid lesions.
The kinetic data derived from the current study demonstrate
that normal thyroid remnants, salivary glands, and tumoral
lesions (residual cancer tissue and metastatic foci) have dif-
ferent kinetic profiles. Sequential 124
I images consistently
demonstrated that the maximum activity within the thyroid
remnant occurs at 24 hours and, after the peak activity is
reached, the clearance is mono-exponential. Physiologic sali-
vary gland activity also demonstrated a dependable kinetic
pattern reaching a peak at four hours after radioiodine ad-
ministration and the clearance is bi-exponential. Nodal meta-
static disease demonstrated a pattern of uptake that was
significantly different from the thyroid remnant or physiologic
salivary gland activity. A protracted retention was identified as
a characteristic pattern for metastatic nodal disease.
The notable variation in individual kinetic parameters
suggests that dosimetry with 124
I PET/CT could enhance the
theranostic value that is always emphasized more than the
traditional 131
I methodology. The decision making and se-
lection of appropriate therapeutic activities of 131
I could be
more reproducible and accurately determined with 124
I. It is
well known that 131
I has many drawbacks as an imaging
agent emitting high-energy 364 keV photons, which are too
high for standard nuclear medicine gamma cameras. The low
count detection sensitivity resulting from penetration of the
crystal and collimator septa by the high-energy photons
causes image degradation. These shortcomings of 131
I con-
ventional gamma camera imaging are overcome by the im-
proved spatial resolution of coincidence detection in 124
I
PET/CT. The higher spatial resolution of 124
I PET/CT is the
basis for improved quantitation. Furthermore, the four-day
half-life of 124
I allows for time sequence imaging, which is
essential for dosimetry applications. The visual image analysis
in this study demonstrated that clinically relevant information
as to the extent of disease can be obtained within a 72-hour
time period. A future detailed dosimetric analysis will finalize
a clinically applicable and logistically feasible protocol (not
demanding on patient and physician time and resources).
Table 2. Comparative Diagnostic Efficacy,
and By-Lesion Uptake Characteristics
of Diagnostic 124
I, Post-Treatment 131
I, and FDG
Lesion definition 124
I 131
I FDG
Neck, remnant, right + + -
Neck, remnant, left + + -
Neck, remnant, right + + -
Neck, remnant, pyramidal + + -
Neck, remnant, pyramidal + - -
Neck, remnant, midline + + -
Neck, remnant, left + - -
Neck, remnant, left + + -
Neck, remnant, left + + -
Neck, remnant, midline + + -
Neck, remnant, midline + + -
Neck, node, L5, right + - +
Neck, node, L5, right - - +
Neck, node, L5, left + - -
Neck, node, L4, right - - +
Neck, node, L3, right + + -
Neck, node, L3, right + - -
Neck, node, L3, left + + -
Neck, node, L3, left + + +
Neck, node, L2, right + - -
Neck, node, L2, left - - +
Neck, node, L2, left + + -
Neck, node, L2, right + - -
Neck, node, L1, left + - -
Neck, node, L1, left + - -
Neck, L6, left + + -
Neck, L6, left + + -
Neck, L6, left + + -
Neck, L6, left + + -
Neck, L6, midline + + -
Neck, residual disease, left + + +
Neck, residual disease, right + + +
Neck, residual disease, right + + -
Sup med, residual disease, right + - -
Sup med, node, right + + -
Sup med, node, right + + +
Sup med, node, midline - - +
Hilar, node, right - - +
Lung, nodule, right - - +
Lung, micronodular disease, bilat - + -
Lung, micronodular disease, bilat - + +
Lung, macronodular disease, bilat - + +
Lung, macronodular disease, bilat + + -
Abdomen, peritoneal + - +
Abdomen, nodal + - +
Abdomen, liver + + +
37/46 28/46 16/46
Table 3. The Comparative Sensitivity Figures
for Diagnostic 124
I Versus Post-Treatment 131
I
TP TN FP FN Sensitivity
124
I 37 6 — 3 92.5%
131
I 28 6 — 12 70%
124
I PET/CT IN THYROID CANCER 445

6. The present data reveal that on a by-patient basis, the mere
presence of remnant tissue can be demonstrated on 124
I pre-
ablation imaging comparable to post-ablation 131
I imaging.
However, 124
I imaging was clearly superior, providing ex-
quisite details in terms of location and laterality of the rem-
nant tissue. High pyramidal lobe remnants were identifiable
by 124
I, but not by 131
I. 124
I was also superior in the distinc-
tion between nodal versus remnant tissue. Perhaps one of
the most important findings obtained was the identification
of functional thyroid tissue without an anatomic depiction/
appreciation of remnant tissue. In all eight patients who had
124
I imaging performed postoperatively, functional thyroid
tissue (remnant) was demonstrated with a measurable func-
tional volume. None of these patients had an anatomically
definable volume of tissue by CT imaging in the thyroid bed.
The functional remnant volume was different for each lobe
(side), in addition to the absolute uptake value at 24 hours, as
well as the clearance, and thus the cumulated activity. This
finding could challenge the recent trend to utilize fixed and
low(er) administered activities to ablate the thyroid remnants
(24–26). Obviously, a larger-scale remnant dosimetry study
is required to address this concern.
Diagnostic 124
I PET/CT imaging failed to demonstrate lung
metastases clearly in three patients, two with micronodular
disease and one with macronodular disease. All of these cases
of lung metastases were detected on the post-treatment 131
I
scans. The discrepancy in regards to detection of micronodular
lung disease may at least in part be explainable by the frac-
tional uptake that could be under the threshold of detectability/
visibility, in the individual nodules from an administered ac-
tivity of 2 mCi 124
I. Visibility threshold is defined as adequate
activity concentration within a given target volume high en-
ough to be discernable from the background activity. Ob-
viously, the fractional uptake of RAI within a lesion is a
function of the NaI symporter (NIS), its expression, and its
temporal and spatial functional activity. Taking into consid-
eration the observation of a protracted retention of radioiodine
in metastatic lesions and given the process of physical decay, it
is possible that these two dynamic processes (in opposing di-
rections) reach the detectability/visibility threshold at different
time points. Not only is the administered activity higher for the
post-treatment 131
I versus diagnostic 124
I scans, there is also a
50% difference in physical half-life between the two radio-
tracers. Therefore, at any reference time point, the relative
cumulated activity will be higher with 131
I. In addition, it was
observed that there is a progressive increase in activity in
metastatic lesions over time. It is postulated that the visibility
threshold may not be reached with a 2 mCi administered ac-
tivity of 124
I because the point of intersection of the time ac-
tivity curve for the tumor and the effective half-life curve for
124
I might remain under the detection threshold.
In one patient, who was proven to have multiple mesenteric/
peritoneal nodules by surgical exploration, the pre-treatment
124
I imaging demonstrated intense uptake in all metastatic
lesions. These lesions were not seen on post-treatment 131
I
images (which also included SPECT). In this particular pa-
tient, a metastatic liver lesion was seen in both imaging
modalities (124
I and 131
I). This perhaps could also be ex-
plained by the temporal and spatial functional activity of NIS,
which may vary at different metastatic sites or lesions.
The issue of NIS activity has a pivotal importance in the
design of the study as well as the data analysis. The functional
dedifferentiation process (in thyroid cancers of follicular cell
origin) involves downregulation of NIS, and therefore not all
thyroid cancer lesions show similar avidity for RAI (27–29). For
this reason, in a strict sense, a FN designation in a given lesion
may not (does not) apply. Similarly, other tissues expressing
NIS will be positive on RAI imaging, and a FP designation for
those does not apply. The sensitivity of 124
I, as a function of
lesionsize,isbestevaluatedbycomparisontothepost-treatment
131
I scan, which typically is performed with administered ac-
tivities >100 mCi. A discordance between the two RAI images
(124
I and 131
I) will indicate a different technical performance of
the respective radiopharmaceutical/imaging technology. A
discordance between RAI images (124
I or 131
I) and F-18 FDG,
on the other hand, will indicate a different functional profile.
124
I imaging is not without potential technical challenges.
The physical characteristics of 124
I compared with 131
I are
summarized in Table 4. One important technical consideration
as it directly applies to clinical imaging performance is that 124
I
has a complicated decay schema. First andforemost, 124
I is not a
pure positron emitter. Thus, a potential factor that may degrade
image quality is an aberrant source of ‘‘true coincidences.’’ In
addition to positron emission, 124
I has prompt gamma-ray
emission that can directly fall within the 511-keV energy win-
dow, or down-scatter and result in signal detection within this
window. The consequence of prompt gamma-ray emission is
that they provide an aberrant source of ‘‘true coincidences’’
when one of the two co-linear 511-keV photons is absorbed or
otherwise notdetected. However, these coincidences contain no
information about the origin of the source decay (30,31). The
contribution of this aberrant coincidence detection and its rel-
evance to clinical imaging/dosimetry is yet to be determined.
Another potentially important technical consideration is the
‘‘spillover effect.’’ The spillover effect can be defined as an
apparent gain in activity for small objects or regions. Although
partial volume effect and spillover essentially refer to the same
physical phenomenon, it is important to distinguish the out-
come of these two different effects. For partial volume effect,
the apparent loss of activity in the object is distributed across
adjacent voxels, which are considered outside the object, re-
sulting in increased activity in these voxels. This increase in
activity is referred to as spillover, whereas loss in activity is
referred to as partial volume loss (32). In 124
I PET/CT imaging
of thyroid remnants and cancers, this effect could be very
important. Remnant tissue, having normal thyroid function,
Table 4. The Physical Characteristics
of 124
I Compared with 131
I
124
I 131
I
Physical half-life 4.2 days 8.02 days
Emissions Gamma
>90% abundance
Gamma
364 keV
81% abundanceMax energy
603–1691 keV
Beta +
23% abundance
Beta -
606 keV max
89% abundanceAverage energy
366–974 keV
Production Cyclotron Reactor
Estimated cost $500/mCi $5/mCi
446 GULEC ET AL.

7. has a preserved capacity of RAI uptake. A very small volume,
undiscernible by CT, may have significant uptake of RAI. By
virtue of the ‘‘spillover’’ effect, the visible PET activity might
be overly exaggerated. In contrast to the remnant tissue, a
small metastatic deposit with suppressed uptake function may
not be appreciated due to partial volume effect.
Conclusion
In conclusion, 124
I PET/CT is a valuable clinical imaging
tool/agent, in both extent of disease evaluation in the setting of
metastatic DTC and in the functional volumetric and kinetic
evaluation of target lesions. On a by-lesion and by-patient
analysis, 124
I clearly demonstrated superior clinical charac-
teristics by identifying 22.5% more foci of RAI-avid lesions
with a sensitivity of 92.5% (compared with the gold standard
131
I post-treatment scan) and by providing exquisite detail in
terms of location and laterality of the remnant thyroid tissue
(even when no remnant tissue was appreciated on anatomical
imaging). 124
I, by virtue of being a PET agent, provides dis-
criminating visual image details, which not only facilitate
detection and visualization of disease, but also potentially
affords quantitative input for accurate dosimetry. The present
study demonstrates different kinetic profiles for normal thy-
roid remnants, salivary glands, and metastatic lesions, as well
as individual variations in functional volumes, and thus cu-
mulated activities, which may have implications for treatment
planning. The quantitative power of 124
I PET/CT can be op-
timized by modifying image acquisition settings and creating
indication-specific (remnant vs. disease imaging) protocols.
Acknowledgments
This study was supported by the Simpkins Foundation
Grant for thyroid cancer research.
Author Disclosure Statement
None of the study authors has competing financial interests
in connection with the submitted manuscript.
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Address correspondence to:
Seza A Gulec, MD
Florida International University
Herbert Wertheim College of Medicine
11200 SW 8 Street, AHC4 284
Miami, FL 33199
E-mail: sgulec@fiu.edu
448 GULEC ET AL.