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Endocrine Care |
Departments of Medicine (A.S.A., A.A.-H., A.A.), Radiology (S.B.), Surgery (M.A.M.), and Biomedical Physics (A.A.H.), King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia
Address all correspondence and requests for reprints to: Dr. Ali Alzahrani, Department of Medicine (MBC-46), King Faisal Specialist Hospital and Research Center, P.O. Box 3354, Riyadh 11211, Kingdom of Saudi Arabia. E-mail: aliz{at}kfshrc.edu.sa
Abstract
Radioactive iodine (131I) plays a major role in the diagnosis and management of differentiated thyroid cancer (DTC); however, data on the use of the 123I isotope in DTC are limited. We compared 238 diagnostic whole body scans performed 24 h after oral ingestion of 185–555 MBq 123I with their corresponding 131I posttherapy whole body scans obtained 4–5 d after 131I therapy. We studied scans in 3 clinical situations: with the first 131I therapy, with the second 131I therapy, and in cases of elevated Tg and negative diagnostic scan. One hundred and seventy-seven pairs were obtained with the first 131I therapy and showed complete concordance between pretreatment and posttreatment scans in 166 pairs (concordance rate, 93.8%). Six other posttreatment scans showed more foci in the thyroid bed than the pretreatment scans, but no evidence of uptake in new areas. Only 5 posttreatment scans showed foci in new locations: 3 in cervical lymph nodes (CLN), 1 in the lung, and 1 new bone metastasis in a patient with known skeletal metastases. With the second 131I therapy, 34 pairs were obtained and showed complete concordance in 28 pairs (concordance rate, 82.4%). Five discordant pairs showed additional foci in areas that were already positive on pretreatment scans. Only 1 posttreatment scan showed a new bone metastasis in a different site from the bone metastases that were seen on its corresponding pretreatment scan. Of 27 pairs of scans in patients with elevated Tg and negative pretreatment scans, 15 posttreatment scans remained negative, 6 posttreatment scans showed an uptake in the thyroid bed, and 3 other posttreatment scans showed lung uptake in patients whose computed tomography scans of the chest showed only bronchiectasis (in 2 patients) and lung scarring (in the third patient) without evidence of lung metastases. Three posttreatment scans showed definite uptake (in thyroid bed, thyroid bed and lung, and CLN) compared with their corresponding pretreatment scans, which were initially reported negative but were retrospectively thought to have had faint uptake. In 56 pretreatment scans, the 123I diagnostic activity was 185 MBq, and the results showed complete concordance in 54 pairs. Two posttreatment scans showed additional uptake: 1 in the bone and 1 in CLN. These data suggest that pretreatment scanning using 123I is highly comparable to 131I posttreatment scanning and that 123I is an excellent diagnostic agent in DTC.
IN DIFFERENTIATED THYROID cancer (DTC),
radioactive iodine (131I) is used postoperatively
for diagnostic whole body scanning as part of monitoring for recurrence
of the disease, for ablation of remnant thyroid tissue, and for
treatment of recurrent and metastatic disease. Its use is based on the
premise that thyroid tissue, whether normal or neoplastic, has the
ability to trap and organify iodide. 131I emits
both ß- and 
-radiation (1, 2). The ß-radiation has
a lethal effect on follicular thyroid cells. For this reason,
131I is used in large administered therapeutic
activities for ablation and treatment of DTC. On the other hand, there
has been a growing concern that the use of 131I
in small activities (111–370 MBq) for diagnostic scanning has a
sublethal effect that renders the tumor tissue less avid for subsequent
131I treatments (3, 4, 5). This
phenomenon has been called stunning effect. It has been shown to occur
with 131I activities as low as 111 MBq
(3). Lower doses of 131I (74–111
MBq) may minimize the stunning effect (6), but may also
decrease the sensitivity of the diagnostic whole body scanning
(4, 7, 8). In contrast to 131I,
123I is considered an ideal isotope for in
vivo diagnostic studies of the thyroid function and structure
(1, 2). It emits only -radiation and thus lacks the
stunning effect (3). It has a short half-life (13 h),
which leads to rapid clearance of background activity. These and other
radiopharmaceutical properties suggest that 123I
might be a better isotope for diagnostic scanning in patients with DTC.
However, experience with 123I in DTC is limited.
To our knowledge, there have been only limited data that have attempted
to assess the diagnostic utility of 123I whole
body scanning in DTC (9, 10, 11, 12, 13, 14). At our institution for the
last 10 yr we have been routinely using 123I for
diagnostic whole body scanning in the follow-up of patients with DTC.
Our experience suggests that this isotope has a high diagnostic utility
in DTC.
In most centers posttreatment scans are routinely obtained after the delivery of large therapeutic activities of 131I for either thyroid remnant ablation or treatment of recurrent or metastatic disease. It has been found that these posttreatment scans are more sensitive than pretreatment 131I whole body scans using diagnostic activities of 74–370 MBq (6, 15, 16). New metastatic foci that are not seen on pretreatment scans appear in about 10% of cases (15), and the pre- and posttherapy scans are different in about 25% of cases (8, 15). Furthermore, in patients with elevated Tg and negative diagnostic whole body scans, posttreatment scans are likely to show areas of iodine uptake, indicating sites of recurrent or metastatic disease (8, 17, 18, 19). Thus, one could consider posttreatment scanning a gold standard imaging technique against which other modalities of scanning should be compared. In this study we sought to evaluate the diagnostic utility of 123I in the follow-up of patients with DTC. For this purpose we compared diagnostic pretreatment whole body scanning using 123I with 131I posttherapy whole body scanning.
Materials and Methods
We compared a total of 238 pairs of pretreatment scans with their corresponding posttreatment scans performed between 1990 and 1999. The selection of scans was based on all of the following criteria: 1) patients had a definite diagnosis of DTC; 2) total or near-total thyroidectomy was performed; 3) TSH level before 123I diagnostic scanning and 131I of more than 30 mU/liter; and 5) pretreatment and posttreatment scans were performed within 10 d of each other. The medical and radiological reports of 177 DTC patients who received 1 or 2 therapies (34 patients) of a large administered activity of 131I (median activity, 4512 MBq; range, 2516–7400 MBq) were reviewed. In addition, we compared 27 pairs of pretreatment and posttreatment scans (median dose, 5994 MBq; range, 5550–7844 MBq) in patients with elevated Tg (median Tg level off thyroid hormones, 171 µg/liter), but negative pretreatment scans. At our institution the administered therapeutic activity of 131I is decided empirically based on the following criteria: when the diagnostic pretherapy 123I whole body scan shows an uptake limited to the thyroid bed, the administered activity ranges between 1850–5550 MBq depending on other prognostic data; if cervical lymph node (CLN) metastases are found, the administered activity ranges between 3700–5550 MBq; and when there is evidence of distant metastases or the patient has Tg-positive, scan-negative disease, the administered activity is 5550–8140 MBq.
Tg was measured by two methods. Between January 1990 and August 1997, a double antibody RIA method was used, with a lower limit of detection of 2.6 µg/liter (EURO/Diagnostic Products, Gwynedd, UK); after September 1997, a chemiluminescent immunometric assay was used, with a lower limit of detection of 0.2 µg/liter (Immulite Kit, EURO/Diagnostic Products). Before September 1997, Tg autoantibodies were not routinely measured; however, as of September 1997, Tg autoantibodies were routinely screened in the same samples in which Tg was measured using a solid phase, two-step, chemiluminescent enzyme immunometric assay with a calibration range up to 3000 IU/ml (Immulite Kit, EURO/Diagnostic Products).
Scans
In preparation for pretreatment diagnostic
123I whole body scans and
131I therapy, patients were kept off
L-T4 for at least 4 wk and off
T3 for at least 2 wk. Patients were prescribed
low iodine diet for at least 1 wk before obtaining pre- and
posttreatment scans. Two diagnostic 123I
activities were used. Between January 1990 and December 1993, the
diagnostic activity used was 185 MBq; however, because of the easy
access of obtaining 123I (our institution has a
cyclotron), the lack of stunning effect, and the potential improvement
in the rate of detection of metastatic disease,
123I scanning activity was increased to 370–555
MBq as of January 1994. 123I was given in the
form of a drink, whereas 131I was given in the
form of capsules. The scanning was performed 24 h after oral
ingestion of 123I diagnostic activities. As a
large proportion of our patients live outside the city where our
institution is located and as a matter of convenience for the patients,
the posttreatment scanning was performed 24–48 h after discharge from
131I therapy (on the average, 4–5 d after the
administration of 131I therapy). Both
pretreatment and posttreatment scans were obtained within a maximum of
10 d of each other. Both types of scans included planar whole body
scanning and dedicated films of the neck and chest regions. The reading
of the scans was limited to three North American-trained nuclear
medicine radiologists with extensive experience in the diagnosis and
therapy of DTC. To avoid bias in the readings of the scans, we used
retrospective radiological reports that were dictated at the time of
performing scans for the purpose of routine management of the patients,
rather than rereading of the films for the sake of this study. The
reason for following this approach is that we believe that a nuclear
medicine radiologist who reads scans for the purpose of routine patient
management is less likely to be biased than when he reads for the
purpose of research study. All pretreatment scans were reported before
131I therapy. After 131I
therapy, posttreatment scans were reported separately. Any findings
that were not noticed on the original reading of pretreatment scan but
were retrospectively noticed when the posttreatment scan was compared
with its corresponding pretreatment scan would be indicated on the
report of the posttreatment scan (the computer software would not allow
editing of an already transcribed pretreatment scan report). In this
study we considered the pretreatment scan readings as entered on the
original report to be the primary result by which we calculated the
concordance rates. However, we pointed out any differences between the
two scans whenever indicated on the posttreatment scan report (see
examples in Table 2
).
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The concordance rates were calculated as follows: number of concordant scans/total number of scans compared x 100. The test between 2 proportions was used to compare the concordance rates between the 185 and 370–555 MBq 123I diagnostic activities used with the first 131I therapy. Because of the small size of the sample in the case of second therapy and therapy for Tg-positive, scan-negative disease, Fisher’s exact test was used to compare concordance rates between 185 and 370–555 MBq 123I diagnostic activities in these situations. The t test was used to examine whether 131I therapeutic activities used in cases of discordant scans were higher than those used in cases of concordant scans. The data are expressed as the median and range or as indicated.
Results
Patients’ characteristics
The scans of 204 DTC patients were studied (41 males and 163 females; median age, 37 yr; range, 7–83 yr). One hundred and seventy-one cases had papillary thyroid cancer (PTC), 25 cases had the follicular variant of PTC, 2 cases had the tall cell variant of PTC, 2 cases had the columnar cell variant of PTC, and 4 cases had follicular thyroid carcinoma. All patients underwent total or near-total thyroidectomy with or without modified neck dissection. One hundred and fourteen patients (55.9%) were in pTNM stage I, 31 patients (15.2%) were in stage II, 18 patients (8.8%) were in stage III, and 4 patients (1.9%) were in stage IV. Thirty-seven patients (18%) could not be classified due to the lack of information on tumor size or perithyroidal tumor extension.
Comparison of first pretreatment and posttreatment scans (177 pairs)
One hundred and sixty-six pairs of scans were concordant (Table 1), showing similar uptake
(concordance rate, 93.8%). The sites of uptake are detailed in Table 1, and examples of concordant scans are shown in Figs. 1 and 2.
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Comparison of second pretreatment and posttreatment scans (34 pairs)
Thirty-four patients had second pretreatment 123I
scans followed by second 131I treatments. Before
scanning and therapy, the median serum Tg and TSH levels were 13.6
µg/liter (4–77 µg/liter) and 175.6 mU/liter (89–445.1 mU/liter)
respectively. Twenty-eight pairs (82.4%) of scans were concordant
(Table 1
), showing similar uptake (Fig. 3). Six posttreatment scans showed
additional foci as follows. Two posttreatment scans each showed a new
focus in the thyroid bed, with their corresponding pretreatment scans
showing lung metastases only. Two posttreatment scans showed additional
uptake in CLN, with their corresponding pretreatment scans already
showing CLN metastases. One posttreatment scan revealed an additional
focus in the lung, with the pretreatment scan already showing lung
uptake. One posttreatment scan showed additional uptake in the bone. In
four of these six discordant pairs, the additional foci that were seen
on posttreatment scans are in areas that already show uptake on
pretreatment scans and consequently probably have little therapeutic
implication.
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Twenty-seven pairs were compared (Table 2). The median Tg level before
pretreatment scans and 131I therapy was 169.7
µg/liter (12–1350 µg/liter). The corresponding median TSH was
119.7 mU/liter (92–259 mU/liter). In 15 pairs, both pre- and
posttreatment scans were negative. In 6 other pairs with negative
pretreatment scans, posttreatment scans showed uptake in the thyroid
bed (Fig. 4). Two patients had negative
pretreatment scans and positive lung uptake on posttreatment scans
(Fig. 5); however, these patients had
bronchiectasis and computed tomographic (CT) scans of the chest did not
demonstrate clear evidence of metastases (probably false positive).
Another patient with a negative pretreatment scan but questionable lung
activity on posttreatment scan showed only lung scarring on CT scan of
the lungs. In 3 patients with faint uptake, which was diagnosed only on
retrospective review of their pretreatment scans, posttreatment scans
showed clear uptake: 1 in the thyroid bed, 1 in the thyroid bed and
lungs, and 1 in CLN.
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A diagnostic 123I activity of 185 MBq was
used in 56 pretreatment scans performed between January 1990 and
December 1993. Comparison of these scans with their corresponding
posttreatment scans showed the following results: 54 pairs were
concordant (96.4%), 41 pairs showed uptake in the thyroid bed only, 10
showed uptake in the thyroid bed and CLN, and 3 showed uptake in the
thyroid bed and superior mediastinum. Two posttreatment scans showed
additional foci; 1 showed foci in the right femur, with pretreatment
scan showing uptake only in the thyroid bed, and the other showed an
additional focus in CLN, with pretreatment scan revealing uptake in the
thyroid bed and superior mediastinum. The concordance rates in the case
of 185 MBq 123I diagnostic activity were similar
to the concordance rates in the case of 370–555 MBq diagnostic
activities (Table 3).
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In 12 cases, posttreatment scans showed uptake that was not seen on pretreatment scans. These foci were thought to represent physiological uptake rather than areas of metastases. This probable physiological uptake was in the form of diffuse liver uptake in 8 cases, diffuse breast uptake in 3 cases, and uptake in the right orbital region of 1 patient. On follow-up, none of these patients showed any other evidence of disease in these areas.
Overall comparison between pre- and posttreatment scans (238 pairs)
Of 238 pairs of scans (Table 4), 209
pairs were concordant (87.8% concordance rate). Of the 29 discordant
pairs, 13 posttreatment scans (5.5%) demonstrated additional foci of
uptake at sites that were already positive on pretreatment scans. These
additional foci are unlikely to have changed the management and are
practically concordant with their corresponding pretreatment scans.
This would increase the concordance rate to 93.3%. Only 16 (6.7%)
posttreatment scans showed additional sites of uptake that may have
affected the management (see above).
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Discussion
In this study we have demonstrated that diagnostic scanning using 123I isotope is highly comparable to high dose 131I posttreatment scans. We have studied this diagnostic isotope in 3 clinical situations: with the first 131I ablative therapy, with the second 131I therapy, and in the case of high Tg and negative diagnostic pretreatment scan. In the case of the first 131I therapy, of 177 pairs compared, 166 pairs were concordant, showing similar distribution of uptake on both pre- and posttreatment scans (concordance rate, 93.8%). In the other 11 discordant pairs, 6 posttreatment scans showed more foci in the thyroid bed than those seen on pretreatment scans; however, there was no evidence of uptake in new regions. Therefore, in essence, those 6 pairs of scans were nearly concordant except for a few more foci in an already positive area (thyroid bed). This is unlikely to have changed the therapeutic dose of 131I or subsequent management. If one considers these new foci to have little clinical significance and those pairs of scans to be concordant, this would increase the concordance rate to 97.2%. Only 5 posttreatment scans (2.8%) showed foci in areas that were not seen on pretreatment scans.
In 34 scan pairs obtained with the second 131I therapy, 28 pairs were quite similar (concordance rate, 82.4%). Six posttreatment scans showed additional foci. In 5 of those discordant pairs, the additional foci were in areas that have obvious uptake on pretreatment scans. Again, this is unlikely to have changed the administered therapeutic 131I activity and the subsequent management. Considering that these new foci have little implication on management, this would increase the concordance rate with the second 131I therapy to 97.1%. Only 1 posttreatment scan showed a new bone metastasis that was not seen on the pretreatment scan of a patient with known bone metastases; therefore, even in this case it is unlikely that finding an additional site of bone metastasis would have changed the management.
In the case of Tg-positive, scan-negative DTC, 46% of the posttreatment scans became positive, showing areas of uptake that were not apparent on pretreatment scans. Indeed, 3 other posttreatment scans that showed lung uptake might have been false positive scans, as CT scans of the chest showed evidence of bronchiectasis in 2 patients and only lung scarring in the third one without clear evidence of lung metastases. Inflammatory lung diseases such as bronchiectasis are recognized to occasionally be associated with false positive lung uptake in patients with DTC (20, 21). If the uptake in these 3 scans represents false positive uptake, then only 7 of 21 (33%) scans were truly positive. This is in sharp contrast to previous studies. Pacini et al. (17) reported positive posttreatment scans in 16 of 17 patients treated with high 131I doses (2775–5180 MBq) for elevated Tg and negative pretreatment scans. Similarly, Pineda et al. (18) reported positive results in 29 of 35 posttreatment scans obtained in 17 patients treated 1–3 times with high dose 131I for elevated Tg but negative pretreatment scans. Schlumberger et al. (19) reported that lung metastases were demonstrated only on posttreatment scans in about half of the patients treated with 3700 MBq 131I for high Tg and normal chest x-rays. The low rate of positivity of posttreatment scans in our patients could be related to a higher sensitivity of 123I as a diagnostic isotope, so that those tumors that were not detected by 123I are unlikely to be seen on post-131I treatment. Alternatively, this may reflect highly dedifferentiated tumors that have lost their ability to concentrate iodide (regardless of the isotope used). Another possibility is iodide overload, which was not excluded in our patients. Nevertheless, if these findings are confirmed in a larger series, it may have some implications in terms of deciding on whether to proceed with 131I therapy in patients with negative 123I diagnostic scan and high Tg level. For example, one may choose to follow an expectant course in a patient with high Tg but negative 123I diagnostic scan, considering that there is only about a 30–50% probability of 131I uptake by the tumor tissue.
It has been thought for a long time that the radiopharmaceutical properties of 123I make this isotope an ideal scanning agent for the thyroid gland. However, there is limited experience with its use as a diagnostic agent in DTC. This is probably related to the fact that this isotope is more expensive and less available than the commonly used 131I. 123I has a short half-life of 13 h and no ß emission. These properties account for the relatively low radiation exposure and low background activity, leading to better quality scanning (11). Thyroid uptake and scanning can be determined within 1–24 h after an oral dose. Its photon energy of 159 keV gives high resolution images superior to those obtained with 131I (1, 2).
In contrast to 123I, there has been extensive
experience with 131I. In DTC, diagnostic whole
body scanning using 131I has been reported to
have a sensitivity of 48–80% and a specificity of 96–100%
(22, 23, 24, 25, 26). Its role in the follow-up of patients with DTC
has been found to be complementary to the other marker of the disease
activity, serum Tg (22). Despite its widespread use, it is
not an ideal isotope for scanning (1, 2). It releases
medium energy ß-particles that increase whole body radiation
exposure. It also releases high energy -rays, which are less ideal
for scanning than the -rays emitted by 123I.
Its 8-d half life, however, allows for scanning over several days.
The 123I diagnostic activities used in this study are relatively high (185–555 MBq). This may have led to better concordance between pre- and posttreatment scans. However, in the analysis of a subgroup of 56 scan pairs that were performed using 185 MBq 123I diagnostic activity (see Results), the concordance rate was similar to the concordance rate in the case of scans performed using 370–555 MBq. In a recent study 123I doses as low as 55.5 MBq with scanning at 5 h were reported to be superior to 131I whole body scanning using 111 MBq for remnant ablation (11). In this study of 35 foci of uptake seen on 123I pretreatment scans performed in 14 patients with DTC, only 32 foci (91%) were visible on 131I pretherapy scans performed about 48 h after the administration of 111 MBq 131I. The researchers commented on the superior quality of 123I images compared with 131I scans (11). In this study scanning was performed 5 h after administration of 123I; other studies reported that pretreatment scanning using 55.5 MBq 123I diagnostic activity with scanning at 24 h was equal or superior to imaging at 5 h for both lesion detection and image quality (12, 13). The researchers suggested, however, that higher diagnostic activity of 74 MBq may be required to improve diagnostic confidence when evaluating negative diagnostic pretreatment scans (13). On the other hand, another small study in which diagnostic whole body scans using 74 MBq 123I activity were compared with diagnostic whole body scans using 74–296 MBq 131I activities concluded that diagnostic scanning using 123I is probably less sensitive for the detection of DTC recurrence than routine 131I diagnostic scanning (14). Thus, further studies are needed to determine the lowest but most effective 123I diagnostic activity needed to decrease costs, on the one hand, but maintain high sensitivity and specificity, on the other hand.
In conclusion, 123I isotope is an excellent scanning agent in the follow-up of patients with DTC and is highly comparable to post-131I therapy scanning using large doses of 131I.
Footnotes
This work was presented in part at the 82nd Annual Meeting of The Endocrine Society, Toronto, Canada, June 2000.
Abbreviations: CLN, Cervical lymph nodes; CT, computed tomographic; DTC, differentiated thyroid cancer; PTC, papillary thyroid cancer.
Received February 26, 2001.
Accepted August 7, 2001.
References
This article has been cited by other articles:
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 K. P. Donahue, N. P. Shah, S. L. Lee, and M. E. Oates Initial Staging of Differentiated Thyroid Carcinoma: Continued Utility of Posttherapy 131I Whole-Body Scintigraphy Radiology, March 1, 2008; 246(3): 887 - 894. [Abstract] [Full Text] [PDF]
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 W. J. Kuijt and S. A. Huang Children with Differentiated Thyroid Cancer Achieve Adequate Hyperthyrotropinemia within 14 Days of Levothyroxine Withdrawal J. Clin. Endocrinol. Metab., November 1, 2005; 90(11): 6123 - 6125. [Abstract] [Full Text] [PDF]
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 S. D. Sarkar, T. P. Kalapparambath, and C. J. Palestro Comparison of 123I and 131I for Whole-Body Imaging in Thyroid Cancer J. Nucl. Med., May 1, 2002; 43(5): 632 - 634. [Abstract] [Full Text] [PDF]
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