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From the Nuclear Radiology Section, Department of Radiology (K.P.D., N.P.S., M.E.O.) and Section of Endocrinology, Diabetes, and Metabolism, Department of Medicine
(S.L.L.), Boston Medical Center and Boston University
School of Medicine, 88 E Newton St, Boston, MA 02118.
From the 2004 RSNA Annual Meeting. Received August
22, 2006; revision requested October 27; revision received May 8, 2007; accepted June 11; final version accepted August 8. Address correspondence to M.E.O.
(e-mail: [email protected]).
Purpose:
To retrospectively compare pretherapy iodine 123 (123I)
and posttherapy iodine 131 (131I) sodium iodide wholebody scintigraphy of patients with newly diagnosed differentiated thyroid cancer to determine if there is significant
and clinically relevant discordance of nonphysiologic iodide-avid foci (IAFs) between the two examinations.
Materials and
Methods:
This study was approved by the Institutional Review
Board, the requirement for informed consent was waived,
and the study complied with HIPAA. The authors identified
108 patients (88 women, 20 men; age range, 16 – 86 years;
mean, 47.5 years; 45 patients younger than 45 years, 63
patients 45 years and older) who previously had undergone total or near-total thyroidectomy for differentiated
thyroid carcinoma. Each patient had undergone a pretherapy 123I whole-body scan followed by a posttherapy
131
I whole-body scan. The number and location of IAFs
were recorded on both scans. Data were compared by
using a Wilcoxon signed rank test for paired data and
assessed clinical relevance based on changes in tumor
staging.
Results:
Posttherapy 131I whole-body scans revealed additional
IAFs outside the thyroid bed not detected on pretherapy
123
I scans in 21 (19%, P ⬍ .001) of 108 patients. Nineteen
(90%) of these 21 had IAFs in new locations (P ⬍ .001),
with tumor upstaging of 11 (59%, 10% of total) of those 19
patients; six (55%, 6% of total) of those 11 had scintigraphic patterns consistent with unsuspected metastatic
disease. Concordant scintigraphic patterns were observed
in 87 (81%) of 108.
Conclusion:
In patients with newly diagnosed differentiated thyroid
cancer who had undergone thyroidectomy and 131I ablation, posttherapy 131I whole-body scintigraphy revealed
new IAFs in 18% and clinical upstaging occurred in 10% of
patients compared with pretherapy 123I whole-body scintigraphy. Therefore, posttherapy 131I whole-body scintigraphy provides incremental clinically relevant information
as it helps to establish the true extent of IAFs and may
contribute to altering of staging.
娀 RSNA, 2008
姝 RSNA, 2008
Radiology: Volume 246: Number 3—March 2008
887
䡲 NUCLEAR MEDICINE
Kevin P. Donahue, MD
Nirav P. Shah, MD
Stephanie L. Lee, MD, PhD
M. Elizabeth Oates, MD
ORIGINAL RESEARCH
Initial Staging of Differentiated
Thyroid Carcinoma: Continued
Utility of Posttherapy 131I Whole-Body
Scintigraphy1
NUCLEAR MEDICINE: Posttherapy Scintigraphy and Thyroid Carcinoma Staging
D
ifferentiated papillary and follicular thyroid cancers are unique
neoplasms for which staging is
determined by anatomic extent and age
criteria (1). While less advanced stages
of disease have extremely favorable survival rates, more advanced stages portend a less favorable prognosis (Table 1)
(1). The iodide avidity of these neoplasms, including their metastases, allows noninvasive staging of the disease
by using radioiodine (sodium iodide)
whole-body scintigraphy. Furthermore,
because of its iodide avidity, malignant
tissue can be effectively treated with
specific radiation therapy with iodine
131 (131I).
Traditionally, pretherapy imaging of
differentiated thyroid cancer was performed with a small (typically 1–2 mCi
[37–74 MBq]) dose of 131I, then followed 48 –72 hours later with wholebody scintigraphy. Thereafter, a therapeutic dose (typically 50 –200 mCi
[1850 –7400 MBq]) was given and posttherapy whole-body scintigraphy was
performed 7–10 days later (2–5). The
radioisotope iodine 123 (123I) sodium
iodide has become increasingly available, permitting its routine use in some
institutions (6–8). The use of 123I has
exposed some of the shortcomings of
131
I as a pretherapy scintigraphic tracer
Advances in Knowledge
䡲 There is a significant (P ⬍ .001)
difference in the number of iodide-avid foci (IAFs) identified at
posttherapy 131I whole-body scintigraphy compared with pretherapy 123I whole-body scintigraphy.
䡲 This difference is clinically relevant because posttherapy 131I
whole-body scintigraphy helps to
identify IAFs in new locations and
aids in clinical upstaging in approximately 10% of patients with
differentiated thyroid cancer,
changing prognosis and altering
future management.
䡲 The number of IAFs identified at
pretherapy 123I whole-body scintigraphy is independent of dose
and patient age.
888
that are related to its decay profile (364keV gamma photon and beta emission).
The beta decay that makes 131I an effective radiotherapeutic agent is believed to produce the thyroid tissue
“stunning” effect reported in some
studies (2–4,9–13). This effect may
reduce the efficacy of the subsequent
larger therapeutic dose and may contribute to incomplete eradication of
tumor burden (2–4,9–11). However,
the debate about the existence of stunning remains open, with more studies
failing to demonstrate either tissue
stunning after 131I diagnostic scanning
or the clinical significance of the stunning phenomenon (5,14).
With the use of 123I, clinicians
avoid this controversy, as it has not
been associated with stunning (6).
Furthermore, 123I (energy level, 159keV gamma photon) produces conventional planar images and single photon
emission computed tomographic (CT)
images with higher resolution and improved contrast when compared with
131
I (8). 123I has been shown in several
studies to be equal or superior to 131I
as an alternative pretherapy imaging
tracer for differentiated thyroid carcinoma (13,15–18). However, there are
drawbacks to the use of 123I. Its 13-hour
physical half-life renders images obtained after 24 hours inferior because of
count paucity. Routine images obtained
at 24 hours may be limited by a lower
lesion-to-background ratio, rendering
subtle lesions difficult to detect.
With this 123I paradigm in place, the
effectiveness of posttherapy 131I wholebody scintigraphy has been called into
question (19,20). The earlier protocol
compared the concordance of pretherapy 131I and posttherapy 131I wholebody scintigraphy. With that protocol,
posttherapy 131I whole-body scintigraphy was useful, as it identified (a) additional iodide-avid foci (IAFs), because
the much higher dose and timing of the
scan enhanced the posttherapy foci con-
Implication for Patient Care
䡲 More accurate staging of thyroid
cancer leads to appropriate management and prognosis counseling.
Donahue et al
trast relative to the rest of the body, and
(b) tissue seen as iodide avid (so-called
stunned tissue) on the pretherapy scan,
but not on the posttherapy scan (20–
22). Recent studies that used the new
paradigm of comparing pretherapy 123I
whole-body scintigraphy with posttherapy 131I whole-body scintigraphy have suggested a high degree of
concordance between the two scans
(8,15–18,23). However, the significance
of any discordance and its effect on clinical staging and patient treatment remain uncertain. Therefore, the purpose
of our study was to retrospectively compare pretherapy 123I and posttherapy
131
I whole-body scintigraphy in patients
with newly diagnosed differentiated thyroid cancer to determine if there is significant and clinically relevant discordance of nonphysiologic IAFs between
the two examinations.
Materials and Methods
Patients
Prescriptions for 131I from January 1,
2002, to July 31, 2005, were reviewed
with the approval of our Institutional
Review Board that approved our study.
The requirement for informed consent
was waived, and the study complied
with the Health Insurance Portability
and Accountability Act. Patients were
included in the study if they had a primary differentiated thyroid carcinoma
and had undergone total or near-total
thyroidectomy for initial treatment folPublished online
10.1148/radiol.2463061328
Radiology 2008; 246:887– 894
Abbreviation:
IAF ⫽ iodide-avid focus
Author contributions:
Guarantors of integrity of entire study, all authors; study
concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or
manuscript revision for important intellectual content, all
authors; manuscript final version approval, all authors;
literature research, K.P.D., N.P.S., M.E.O.; clinical studies,
all authors; statistical analysis, K.P.D., N.P.S.; and manuscript editing, all authors
Authors stated no financial relationship to disclose.
Radiology: Volume 246: Number 3—March 2008
NUCLEAR MEDICINE: Posttherapy Scintigraphy and Thyroid Carcinoma Staging
lowed by 131I ablation. Patients with recurrent disease were not eligible. All
patients had a tissue diagnosis of differentiated papillary or follicular thyroid
cancer made by our Pathology Department, or Endocrinology Section records
indicating that the clinician’s diagnosis
was in accordance with the tissue diagnosis made at an outside institution.
Further inclusion criteria required that
pretherapy and posttherapy wholebody scintigraphy had been performed
at our institution by using 131I and 123I,
respectively, and that pretherapy wholebody scans were performed 24 hours after 123I oral administration, and posttherapy whole-body scans were performed 7– 8 days following 131I oral
administration.
Whole-Body Scintigraphic Imaging
All patients were instructed to avoid iodinated intravenous contrast material
for at least 6 weeks and maintain a lowiodine diet for 7–10 days prior to scintigraphic imaging and were prepared for
imaging and therapy with withdrawal
from synthetic thyroid hormone replacement and 30 ␮U/mL (30 mIU/L) or
more of thyroid-stimulating hormone
serum. Women of child-bearing age had
a negative blood pregnancy test within 2
days of 123I administration in anticipation of 131I therapy. At 24 hours prior to
imaging, 123I was administered orally.
The next day, whole-body scanning with
the neck hyperextended was performed
with images acquired in anterior and
posterior projections at a rate of 4 cm/
min by using a dual-detector gamma
camera (ecam; Siemens Medical Solutions, Hoffman Estates, Ill) equipped
with low-energy, high-resolution collimators and peaked at 159 keV with a
15% window. Protocols for the dosing
of 123I varied over the course of this
study from 5 mCi to 1.5–2 mCi (185
MBq to 55.5–74 MBq) as evidence became available that lower doses produced results comparable to those produced with higher doses (7,24).
On the same or next day, therapeutic 131I was administered orally. When
the patient returned 7– 8 days later for
posttherapy 131I scintigraphy, scanning
with the neck hyperextended was perRadiology: Volume 246: Number 3—March 2008
Donahue et al
formed, with images acquired in anterior and posterior projections at a rate
of 4 cm/min by using the same dualdetector gamma camera equipped with
high-energy collimators and peaked at
364 keV with a 15% window. Dosing of
131
I was predicated on the extent of
IAFs observed on the 123I whole-body
scans and the original surgical staging.
Scintigraphic Analysis
Scintigraphic images had been interpreted and reported by one of three
experienced nuclear radiologists (a
nonauthor, N.P.S., and M.E.O., with
30, 3, and 20 years experience, respectively). The radiologists reported
the number and location of abnormal
IAFs on 123I and 131I scans. Radiologists were not blinded to the results of
123
I scans when interpreting 131I scans
and routinely compared them when interpreting the second scan, as is done
in clinical practice.
Data Collection and Staging
Original scintigraphic reports were then
reviewed. The number and location of
IAFs outside the thyroid bed on pretherapy 123I and posttherapy 131I whole-
body scans were recorded and cataloged for each patient (K.P.D. and
M.E.O.) as being located in the regional
lymph nodes, mediastinum, lungs, abdomen, and/or bone. These tabulated
results from the pretherapy and posttherapy scans were then compared
(K.P.D., N.P.S., M.E.O.) to assess discordance (ie, IAFs observed on only one
scan) between the two scans. Doses of
123
I and 131I were recorded (K.P.D.) to
enable the authors to examine the relationship between the dose of radioiodine and the number of IAFs seen at
whole-body scintigraphy. Patient age at
the time of posttherapy 131I scintigraphy, an important criterion in differentiated thyroid cancer staging, was recorded (K.P.D.).
Surgical pathologic and operative
reports were reviewed for patients
found to have discordant 123I and 131I
scan findings. The size of the primary
thyroid tumor, capsular penetration,
extension into surrounding tissues, and
regional nodal involvement were recorded and combined with the results of
the pretherapy 123I scan to provide an
initial staging for this investigation by all
authors of the manuscript through con-
Table 1
Staging Criteria and Observed 5-year Survival Rates for Differentiated Thyroid
Carcinoma
Age and Cancer Stage
⬍ 45 y
I
II
ⱖ 45 y
I
II
III
IVa
IVb
IVc
Size*
Tumor Stage
Location†
Metastasis‡
Cancer Survival Rate (%)
Papillary
Follicular
Any
Any
Any
Any
0
1
97
93
95
90
1
2
1–3
3
1–3
4a
4b
Any
0
0
1a
0
1b
0
Any
Any
0
0
0
0
0
0
0
1
97
93
83
95
90
69
39
41
Note.—Adapted, with permission, from reference 1.
* Size 1 ⫽ ⬍ 2 cm; size 2 ⫽ 2– 4 cm; size 3 ⫽ ⬎ 4 cm; size 4a ⫽ any size tumor with local invasion into subcutaneous
soft tissues, larynx, trachea, esophagus, or recurrent laryngeal nerves; and size 4b ⫽ tumor invades mediastinum or
prevertebral fascia or encases carotid artery.
†
1a ⫽ Prelaryngeal and/or Delphian pre- and/or paratracheal nodes; 1b ⫽ cervical, superior mediastinal nodes.
‡
0 ⫽ No metastasis; 1 ⫽ distant metastasis.
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NUCLEAR MEDICINE: Posttherapy Scintigraphy and Thyroid Carcinoma Staging
sensus. Tumors were then restaged and
categorized in patient age cohorts by
using the results of posttherapy scans
and the age cohorts used in the staging
criteria by all authors through consensus (1). Patients with discordant scans
then had their 123I and 131I dosing data
reviewed to ensure that aberrantly low
doses of 123I were not associated with
aberrantly high doses of 131I, as this
phenomenon would play a confounding
role in the discordance between the
studies.
Statistical Analysis
The outcome variables (differences in
IAFs outside the thyroid bed between
the 123I and 131I whole-body scans) exhibited a distribution with a high frequency of zero values and consequently
could not be reasonably approximated
by using a Gaussian distribution; thus,
nonparametric methods were used. To
assess the significance of differences in
the numbers of IAFs, the Wilcoxon
signed rank test for paired data was
used. This test was used first to test all
discordant studies and then twice more
to test individually for significance in
(a) IAFs in new sites, and (b) additional
IAFs in previously identified sites.
To assess for possible confounding
factors, the dose of 123I, the dose of 131I,
patient sex, and patient age (younger
than 45 years or 45 years and older) for
all 108 patients were examined by using
the Spearman rank correlation coefficient and the ␹2 test for correlation to
the difference in IAFs outside the thyroid bed seen on 123I and 131I scans. A
further confounding effect, that the pos-
Donahue et al
sibility that low doses of 123I were associated with high doses of 131I, was also
addressed by using the Spearman rank
correlation coefficient. This possibility
was evaluated for the entire study population and for the subpopulation of discordant studies. Possible association
between 123I and 131I doses with total
IAFs detected on the respective wholebody scans was assessed by using the
Spearman rank correlation coefficient
in an effort to examine a possible dosefocus relationship. All statistical computations were performed (K.P.D.) in
consultation with a nonauthor biostatistician by using software (SPSS, version
12.0.1; SPSS, Chicago, Ill).
Results
Demographics and Dosing
The medical record review yielded 108
patients who met our study criteria. The
study comprised 88 women and 20 men
(age range, 16 – 86 years; mean, 47.5
years), with 45 patients younger than
45 years and 63 patients 45 years and
older. Patients were administered 123I
with a radioactivity range of 0.7–5.0
mCi (mean, 2.4 mCi [range, 25.9 –185
MBq; mean, 88.8 MBq]) and 131I with a
radioactivity range of 30 –205 mCi
(mean, 122.6 mCi [range, 1110 –7585
MBq; mean, 4536.2 MBq]). Administered doses were in the ranges specified
by protocols in use when the patient
was treated, with the exception of a single dose (0.7 mCi [25.9 MBq]), which
was below the specified limit of 1.5 mCi
[55.5 MBq] for 123I.
Discordant Scans
Comparison of the pretherapy 123I
whole-body scans with the posttherapy
131
I whole-body scans with respect to
IAFs outside the thyroid bed revealed
that all 131I scans showed the foci initially identified on 123I scans (Table 2).
However, this analysis yielded discordant scintigraphic patterns between
pretherapy 123I and posttherapy 131I
scans where additional IAFs were identified on the 131I scan in 21 (19%) of 108
patients (Figs 1–3). These results indicated a significant difference (P ⬍ .001).
Of these 21 patients with discordant
scans, new IAF sites were identified in
19 versus additional IAFs identified in
established sites in two (Table 2).
Independent assessment for significance between the two groups of patients with discordant scans was undertaken. The patients with IAFs in
new locations showed a significant increase in the number of foci (P ⬍
.001); however, those with additional
IAFs at sites previously shown to have
such foci did not attain significance
(P ⫽ .157) (Table 2).
To address the issue of confounding
by other variables, patients with concordant and discordant scans were
compared for the variables of age (P ⫽
.42), 123I dose (P ⫽ .47), and 131I dose
(P ⫽ .13) by using an independent sample t test. The proportion of male patients in the concordant and discordant
groups was also examined (17% vs
23%, ⫻ ⫽ 0.15, P ⫽ .70).
Figure 1
Table 2
Comparison of Pretherapy 123I and Posttherapy 131I Scintigraphic Patterns and
Statistical Analysis of Discordant Foci
Pattern of Foci
All
Concordant, 123I ⫽ 131I
Discordant, more 123I than 131I
Discordant, less 123I than 131I
Foci in new sites
More foci in known sites
Note.—Numbers in parentheses are percentages.
890
No. of Patients
P Value
108 (100)
87 (81)
0 (0)
21 (19)
19
2
...
...
...
⬍.001
⬍.001
.157
Figure 1: Regional scintigraphy of lymph
nodes. (a) Anterior pretherapy 123I scan shows IAF
(arrow) in thyroid bed, consistent with remnant
thyroid tissue. (b) Anterior posttherapy 131I scan
shows remnant tissue (arrow) and reveals new IAF
(arrowhead) that indicates regional nodal disease.
Radiology: Volume 246: Number 3—March 2008
NUCLEAR MEDICINE: Posttherapy Scintigraphy and Thyroid Carcinoma Staging
Donahue et al
Figure 2
Figure 2: Whole-body scintigraphy of lung metastases. (a) Anterior and posterior pretherapy 123I scans show IAF cluster in thyroid bed, consistent with thyroid remnant tissue. (b) Anterior and posterior posttherapy 131I scans show multiple new IAFs (arrows), indicating pulmonary metastases and asymmetric physiologic activity in
oropharynx.
Staging
Staging was undertaken by using the
guidelines for differentiated thyroid cancer promulgated by the American Joint
Commission on Cancer (Table 1) (1).
Of 19 patients with discordant 123I and
131
I scans indicating new IAF sites,
changes in clinical staging were seen in
11 (58%), representing 10% of the total
population (Table 3). Eight of those 19
patients had unsuspected distant IAFs
in the lung or bones.
Staging of differentiated thyroid carcinoma is heavily influenced by patient
age (Table 1). As such, the patients
were divided into age cohorts, those
younger than 45 years and those 45
years and older, and reexamined. The
age cohorts were chosen for their relevance to staging criteria. The cohorts
were similar in size, with 45 (42%) of
108 patients younger than 45 years and
63 (58%) 45 years or older. The incidence of scintigraphic discordance within
these two groups was similar (eight of
45, 18%; 11 of 63, 17%, respectively),
as were the locations where the scintigraphic discordance was noted, with
Radiology: Volume 246: Number 3—March 2008
the exception of bone metastases
(Table 4). However, upstaging was
more common in patients 45 years and
older (eight of 63, 13%) when compared with patients younger than 45
years (three of 45, 7%) (Table 3).
Dose-Dose and Dose-Foci Relationship
There was no significant association between doses of 123I and 131I in the entire
population (r ⫽ ⫺0.13, P ⫽ .16) or in
the subpopulation of discordant studies
(r ⫽ ⫺0.12, P ⫽ .60). Further, doses of
123
I and 131I were not significantly associated with the total number of IAFs
(r ⫽ 0.07, P ⫽ .5; r ⫽ 0.17, P ⫽ .08,
respectively). However, it is noted that
the association of 131I does trend toward significance.
Discussion
In our study, we evaluated differences in
the scintigraphic patterns between pretherapy 123I and posttherapy 131I wholebody scans and found a significant difference (P ⬍ .001) between the IAFs detected on pretherapy 123I and posttherapy
131
I whole-body scans. There were two
groups of patients with discordance: one
group with IAFs in one or more new sites
(n ⫽ 19) and one group with additional
IAFs (n ⫽ 2) in previously identified sites
of disease. The first group was not only
significant (P ⬍ .001), but was also clinically relevant because IAFs in new locations often alter staging. The second
group lacked significance (P ⫽ .157) and
there is no clinical relevance because
additional IAFs in an area of established
foci do not affect staging.
Tumor staging of a patient with differentiated thyroid carcinoma is undertaken with a combination of surgical
and radiographic staging. While surgical pathology greatly influences the process of staging, radiologic imaging is relied on quite heavily (1). Thus, the clinical relevance of the interpretation of a
given study by a radiologist is quite important and affects clinical management. A second round of surgical staging to confirm or disprove the radiographic interpretation of metastatic
nodal or distant disease is not common.
Therefore, radiographic findings do
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NUCLEAR MEDICINE: Posttherapy Scintigraphy and Thyroid Carcinoma Staging
Donahue et al
Figure 3
Figure 3: Whole-body scintigraphy of bone metastasis. (a) Anterior pretherapy 123I scan shows definite
single thyroid bed remnant. (b) Anterior posttherapy 131I scan shows discrete, intense IAF (arrow) in middle
lower thorax. In retrospect, this lesion is subtle and present in a. CT scan corroborated small lytic lesion in
lower sternum.
Table 3
Age-related Incidence of Discordance and Altered Stage with Posttherapy 131I
Scintigraphy
Incidence of Discordance and/or Altered Stage
New foci
Same stage
Altered stage
Altered to stage II
Altered to stage III
Altered to stage IVc
Age ⬍ 45 Years
(n ⫽ 45)
Age ⱖ 45 Years
(n ⫽ 63)
Total (n ⫽ 108)
8 (18)
5 (11)
3 (7)
3
NA
NA
11 (17.4)
3 (4.7)
8 (12.7)
0
3
5
19 (18)
8 (7)
11 (10)
3
3
5
Note.—Numbers in parentheses are percentages. NA ⫽ not applicable.
Table 4
Age-related Biodistribution of New 131I Foci
Age (y)
⬍45
ⱖ45
All
892
Lymph Node
Mediastinum
Mediastinum and Lymph Node
Lung
Bone
Total
2
5
7
2
1
3
1
0
1
3
2
5
0
3
3
8
11
19
lead to changes in clinical staging, as
seen in 11 patients in this study.
Of 21 patients with discordant 123I
and 131I scans, 11 were found to be
clinically upstaged on the basis of a
posttherapy 131I whole-body scan that
showed additional IAFs in new locations when compared with the pretherapy 123I whole-body scan. The
specific changes in patient treatment
brought about by the changes in clinical stage are beyond the scope of this
study, but the changes in prognosis
can be dramatic (Table 1).
It is with this concept in mind that
the comparison between the discordance and clinical changes in age cohorts was undertaken. While the incidence of discordant scans was equivalent between the two age cohorts, the
incidence of upstaging was not, rather it
was more common in patients 45 years
and older (Table 3). This result was not
surprising, as there are more staging
options available for individuals 45
years and older; there is a less onerous
burden to meet criteria for a higher
stage as compared with those younger
than 45 years, where the single criterion is the presence of distant metastatic disease (Table 1). However, while
these results are not surprising, they are
important. The patients 45 years and
older are frequently upstaged higher than
those younger than 45 years, thereby
placing them in stages with lower 5-year
survival rates (Tables 1, 3).
A key feature of our study was its
retrospective nature. It was thought
that use of radiographic reports and
data originally generated for the exclusive purpose of patient care would introduce less bias. Further, these were
the studies used for tumor staging in
patients after initial surgery. As such, it
allowed the authors to state that the
staging changes and associated effect on
expected survival were actual and not
theoretical. The authors did not follow
patients to ensure they conformed to
the reported 5-year survival data as this
was outside the scope of the study.
It has been suggested that the number of IAFs observed on pretherapy 123I
scans may be related to the dose of 123I
given, and by extension, posttherapy
Radiology: Volume 246: Number 3—March 2008
NUCLEAR MEDICINE: Posttherapy Scintigraphy and Thyroid Carcinoma Staging
discordance may be a product of this
dose dependence (16). The data compiled in our study fail to demonstrate a
correlation between the dose of 123I in
our study range (0.7–5 mCi [25.9 –185
MBq]) and the number of IAFs visualized (r ⫽ 0.07, P ⫽ .5). Consequently, it
is unlikely that the significant difference
we observed in IAFs is a product of
decreasing diagnostic dose of 123I over
time. That is, despite our initial use of 5
mCi (25.9 MBq) of 123I and a downward
trend to our current dose of 2 mCi (74
MBq), it is unlikely this trend resulted in
the observed discordance between 123I
and 131I scans. A trend toward significance (r ⫽ 0.17, P ⫽ .08) is noted when
the correlation between the therapeutic
dose of 131I (30 –205 mCi [1110 –7585
MBq]) and the number of IAFs is examined. This result is not surprising, given
that the therapeutic dosage of 131I is
generally chosen on the basis of the extent of IAFs seen at pretherapy scintigraphy and with the original surgical
staging.
Further possible confounding factors were explored and eliminated to
ensure that the significant difference between pretherapy 123I and posttherapy
131
I whole-body scans was as robust as
possible. Patient age (P ⫽ .42), dose of
123
I (P ⫽ .47), dose of 131I (P ⫽ .13),
and patient sex (P ⫽ .7) all lacked significant correlation to the difference seen
in IAFs. Additionally, the doses of 123I
and 131I lacked any significant inverse
correlation among the study population
as a whole and in the subgroup of those
patients with discordant scans (r ⫽
⫺0.13, P ⫽ .16; r ⫽ ⫺0.12, P ⫽ .6,
respectively). This finding is significant
as it indicates that the discordant scans
were not the product of low doses of 123I
followed by high doses of 131I, thereby
producing discordance by means of aberrant dosing patterns.
Some studies have shown greater
concordance between pretherapy 123I
and posttherapy 131I whole-body scans
(12,23). It is important to note that the
purpose, scope, and methods of those
studies differ from ours. Some focused
on the diagnostic role of 123I versus 131I
exclusively, or in part, on the imaging of
recurrent differentiated thyroid carciRadiology: Volume 246: Number 3—March 2008
noma, a group that was explicitly excluded from our study (12,23). Further,
posttherapy 131I whole-body scans were
performed sooner after dosing (23)
than in our study, possibly confounding
results.
Our study was limited in that it reports patients from a single institution,
and thus, the possibility of population
bias exists. Another limitation was that
the data rely on original report quality
and consistency and the inherent difficulty in resolving the exact number and
location of sites of pathologic radioiodine activity. While we recognize these
limitations, it was considered important
that the images not be reinterpreted for
the purpose of this study, as that could
introduce bias and reduce the clinical
applicability of the study. Further, the
staging of differentiated thyroid cancer
does not require exact localization of
distant metastatic disease (Table 1).
Posttherapy 131I scan interpretation was
not blinded to the results of pretherapy
123
I scans. However, this interpretive
process is consistent with clinical
practice. Finally, this study does not
address the relationship of thyroglobulin levels through the course of diagnosis, pretherapy imaging, and posttherapy imaging, as the data were not
available for all patients.
In conclusion, there is a significant
difference in scintigraphic patterns between pretherapy 123I and posttherapy
131
I whole-body scans when evaluating
pathologic IAF outside the thyroid bed.
Discordant scintigraphic patterns may
lead to altered staging; in our study, this
change occurred in 11 (10%) of 108
patients, often with unsuspected distant
metastatic IAF. When using 123I as the
pretherapy imaging tracer, we believe
that posttherapy 131I whole-body scintigraphy should be performed routinely
because it provides clinically relevant
information, especially in patients 45
years and older. Further, it is not the
intent of the authors to imply that pretherapy scans are rendered obsolete, as
they can guide selection of therapeutic
radioiodine dose, given the extent of
metastatic disease and degree of uptake
by the thyroid remnant. The number of
IAFs identified is not significantly re-
Donahue et al
lated to the dose of 123I, but does influence the therapeutic dose of 131I administered, as expected.
Acknowledgment: The authors thank Al Ozonoff, PhD, for his biostatistical help and support.
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Radiology: Volume 246: Number 3—March 2008
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