Diagnostic Performance of 18F-FDG PET/CT in Papillary Thyroid Carcinoma with Negative 131I-WBS at first Postablation, Negative Tg and Progressively Increased TgAb Level

Differentiated thyroid cancer (DTC) patients with negative serum thyroglobulin (Tg), negative 131I whole–body scintigraphy (131I-WBS) at first post-ablation and progressively increased TgAb level are a relatively rare entity in the follow-up after total thyroidectomy and radioactive iodine therapy. The value of 18F-FDG PET/CT in detecting the recurrence of disease in these patients has only been reported in a small case series. The goal of this study was to investigate the diagnostic accuracy of 18F-FDG PET/CT in detecting recurrent disease in these specific PTC patients and to identify risk factors for patients with positive 18F-FDG PET/CT results. Eighty-two PTC patients who had 18F-FDG PET/CT scans with negative Tg, negative 131I-WBS at first post-ablation and progressively increased TgAb levels were included. We found that the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 18F-FDG PET/CT in this patient group were determined as 84%, 72%, 92%, 57% and 82%, respectively. 18F-FDG PET/CT scan had a good diagnostic performance and should be performed routinely in PTC patients with negative Tg, negative 131I-WBS at first postablation and progressively increased TgAb level, especially when span for progressively increased TgAb level ≥ 3 years and/or progressively increased TgAb value up to 150 IU/mL.

Whether or not elevated serum TgAb concentrations can be used as a surrogate marker of persistent or recurrent disease remains controversial 9,10 . Some argued that TgAb levels did not predict disease status in DTC because TgAb production primarily arises in coexisting lymphocytic thyroiditis or Graves' disease in DTC patients 11 . It has been reported that only the progressively increased TgAb level was useful for predicting clinical recurrence or persistence of Tg-negative patients with PTC 12,13 . 18 F-fluorodeoxy-D-glucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) is routinely performed to search for the recurrent or persistent disease in patients with DTC 14 . However, only a few studies including a small case series evaluated the value of 18 F-FDG PET/CT in DTC patients who have negative 131 I-WBS, negative Serum Tg, and increased TgAb titer 15, 16 . In the present study, we aimed to investigate the diagnostic accuracy of 18 F-FDG PET/CT, performed over one year after their first remnant ablation, in detecting recurrent disease of PTC in a relatively large clinical samples of patients with negative Tg, negative 131 I-WBS at first postablation and progressively increased TgAb level. Moreover, we also identified the correlation of clinical and pathological factors with positive 18 F-FDG PET/CT findings in this specific cohort.

Results
Patient's characteristics. According to the inclusion and exclusion criteria, eighty-two PTC patients who underwent 18 F-FDG PET/CT scans with negative Tg, negative 131 I-WBS at first post-ablation and progressively increased TgAb level were confirmed and included. Of them, 58 (71%) PTC patients with serum Tg levels < 0.2 ng/mL (TSH suppression) and 24 (29%) PTC patients with serum Tg levels < 1 ng/mL (TSH stimulation >30 IU/mL) at 6 months after first remnant ablation. Serum Tg levels were always <0.2 ng/mL under TSH suppression for all these patients in the follow-up. The characteristics of the study cohort at diagnosis of recurrent PTC were shown in Table 1. 18 F-FDG PET/CT findings, 59 (72%) patients had results interpreted as positive and 23 (28%) patients as negative. In 59 cases with positive 18 F-FDG PET/CT findings, 54 (91.5%) patients were classified as true-positive confirmed pathologically by surgical specimens (Fig. 1) US was performed in all patients before 18 F-FDG PET/CT scan. 39 patients with 51 lymph node metastases were found in the neck, among which 34 patients with 42 lesions were detected by neck US. Two cases with 2 lymph nodes metastases, one case with 1 lymph node metastasis and 6 cases with 7 lymph node metastases were found in pharyngeal space, parotid, and mediastinum, respectively, all of which were detected by contrast-enhanced CT after 18 F-FDG PET/CT scanning. 4 patients with 18 F-FDG PET lung metastases were diagnosed, all of which were detected and confirmed by chest CT (Table 2). 7 false-positive lesions were found on 18 F-FDG PET/CT scan in 5 patients in the neck, 5 FDG-avid lesions in 4 patients and 2 FDG-avid lesions in 1 patient were diagnosed as reactive infection of lymph node and hyperplasia of lymph nodes (Fig. 2). All these patients had suspicious lymph nodes for recurrence on the neck US. In 23 cases with negative 18 F-FDG PET/CT findings, 10 patients were interpreted as false-negative, among which 13 lymph node metastases from 8 patients were detected in the neck and 2 lymph node metastases from the remaining 2 patients were found in the mediastinum. All the 10 patients with false-negative results received 131 I treatment once again. 2 cases with 2 neck lymph node metastases and one case with 1 mediastinal lymph node metastasis were diagnosed by 131 I-WBS combined with 131 I-SPECT/CT after 131 I treatment. The remaining 7 patients with 10 lesions who had negative 131 I-WBS results were confirmed by surgical pathology. All these patients had suspicious lymph node recurrence on the neck US or contrast-enhanced CT of chest (Table 3).

F-FDG PET/CT finding. Of 82 patients with
Of 13 true-negative patients, neck US finding was suspicious for recurrence in 7 patients with 12 lesions, but disease recurrence was not detected by surgical excision. The remaining 6 patients underwent 131 I treatment once again and negative findings were shown on the 131 I-WBS, and recurrent diseases were not be detected by US neck and chest contrast-enhanced CT in these 6 patients. In addition, bone metastases from PTC weren't detected on the 99m Tc-bone scan, but TgAb levels were gradually rising in the follow-up. These 6 patients were also classified as true-negative.
Factors influencing positive 18 F-FDG PET/CT results. Patient age, sex, subtypes of PTC, tumor size, extrathyroid extension, bilateral tumor, multifocal tumor, whether patient with neck lateral dissection at initial surgery, N stage, whether pathology with lymphocytic thyroiditis not significantly associated with positive 18 F-FDG PET/CT results (P > 0.05). TgAb level at diagnosis and span for progressively increased TgAb level were statistically significant in predicting positive 18 F-FDG PET/CT findings (P < 0.05). Compared with TgAb level <150 IU/mL at diagnosis and span for progressively increased TgAb level less than 3 years, univariate woman underwent total thyroidectomy with central lymph node dissection on the right neck region and radioiodine ablation for remnant PTC and thyroid tissue. 131 I-WBS obtained 5 days after an oral administration of 3.7 GBq of 131 I showed negative finding. Six months after ablation, the patient had negative Tg (<0.1 ng/mL) but abnormal TgAb of 108 IU/mL at TSH suppression status. Subsequently, during the follow-up 3.5 years later, TgAb level progressively increased from 108 IU/mL to 623 IU/mL. 18   Diagnostic accuracy of 18 F-FDG PET/CT scans. In all these patients, the true-positive, false-positive and false-negative, true-negative cases of 18 F-FDG PET/CT findings were 54, 5, 10, and 13, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 18 F-FDG PET/CT in this patient group were determined as 84%, 72%, 92%, 57% and 82%, respectively (Table 5).
When comparing different TgAb levels at diagnosis, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 18 F-FDG PET/CT for patients whose TgAb levels ≥ 150 IU/mL at diagnosis is higher than for those whose TgAb levels < 150 IU/mL at diagnosis. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy increased from 62% to 95%, from 67% to 78%, from 81% to 95%, from 43% to 78% and from 63% to 94% respectively (Table 5). When comparing different span for progressively increased TgAb level, the sensitivity, specificity, positive predictive value, and accuracy of 18 F-FDG PET/CT for span for progressively increased TgAb level longer than 3 years at diagnosis were superior to that less than 3 years at diagnosis, the sensitivity, specificity, positive predictive value, and accuracy of 18 F-FDG PET/CT scan increased from 76% to 91%, from 71% to 75%, from 85% to 97%, from 74% to 90%. However, the negative predictive value of 18 F-FDG PET/CT for patients whose span for progressively increased TgAb level ≥ 3 years at diagnosis was inferior to that <3 years at diagnosis. The negative predictive value decreases from 59% to 50% (Table 5).

Discussion
Our study demonstrated that 18 F-FDG PET/CT was a useful method for detecting recurrent disease in PTC patients with negative Tg, negative 131 I-WBS at first post ablation and progressively increased TgAb level. In the current study, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 18 F-FDG PET/CT for this patient group were confirmed as 84%, 72%, 92%, 57% and 82%, respectively. The diagnostic performance of 18 F-FDG PET/CT scanning for detecting the recurrent thyroid cancer with negative Tg, negative 131 I-WBS and increased TgAb has been reported several retrospective studies [16][17][18][19][20][21] (Table 6). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 18 F-FDG PET/CT examination for these patients ranged from 75% to 100%, from 50% to 100%, from 50% to 100%, from 50% to 100%, from 25% to 100% and from 72.7% to 88.4%. The difference within these several studied may reflect the heterogeneity of the number and patients included, definition of Tg negativity, selection criteria for TgAb level, follow-up time, specific 18 F-FDG PET/CT technique used, or the reference standard against which the accuracy of 18 F-FDG PET/CT scan were analyzed. Among them, five articles have a small number of cases (16,(18)(19)(20)(21), so the results were very easy to produce deviation. The largest 18 F-FDG PET/CT series to date was the retrospective study by Asa et al. and included 40 DTC patients, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy in this large study were 78.5%, 50%, 91.6%, 25% and 75% 21 , all of which lower than those reported by ours. This difference may reflect possibly definition of Tg negativity, selection criteria bias of TgAb and follow-up time. In our study, Negative serum Tg was defined as Tg < 0.2 ng/mL (TSH suppression) or Tg < 1 ng/mL (after stimulation) at 6 months after the first 131 I remnant ablation, while Asa et al. considered that the PTC patients had negative serum Tg level as Tg ≤ 1 ng/mL (TSH suppression) or Tg ≤ 2 ng/mL (after stimulation) in the follow-up period after total-near total thyroidectomy and 131 I ablation 21 . If DTC patients with coexistent clinical Hashimoto thyroiditis Graves' disease, or focal autoimmune thyroiditis, all TgAb disappeared Figure 2. A false-positive lesion on the left neck region was revealed by 18 F-FDG PET/CT. A 62-year-old woman underwent total thyroidectomy with radical left neck dissection for PTC followed by radioiodine therapy with 3.7 GBq of 131 I. Three days later, post-therapy 131 I WBS was performed and showed negative results. Six months after ablation. The serum Tg level was 0.18 ng/mL and TgAb level was 46 IU/mL at TSH suppression status. TgAb level was stable for 4.2 yr after 131 I therapy. But subsequently, TgAb gradually increased at TSH suppression status. TgAb level elevated from 51 IU/mL to 137 IU/mL in the next follow-up of 2.2 years. 18 F-FDG PET/CT demonstrated increased foci radiotracer uptake in the left submandibular region (a,b, crossing line), which was localized by CT image to the left submandibular lymph nodes with SUV max of 2.6 (c, crossing line). However, infectious lymph node was diagnosed on histopathology after surgery.  more slowly and the median disappearance time was 3 years for TgAb after total thyroidectomy and radioiodine ablation 22 . Therefore, increased TgAb level without upward trend in a short follow-up time might not be viewed as persistent or recurrent diseases of DTC. In our cases, increased TgAb level without upward trend has been excluded. Although Asa et al. selected the TgAb standard for persistently/progressive increased TgAb, whether the content of the article including increased TgAb level without upward trend was unclear 21 . Otherwise, it was reported that the TgAb levels measured 6-12 months after ablation therapy were significantly rising in the DTC patients with residual disease compared to those with no residual disease 23 . Whether this situation for DTC patients ruled out was indeterminate for the study by Asa et al. because DTC patients in their groups have relatively short follow-up times (9-36 months). In our study, of 59 cases with positive 18 F-FDG PET/CT finding, 54 (91.5%) patients were classified as true-positive confirmed pathologically by surgical resection and 5 patients were diagnosed for false-positive on 18 F-FDG PET/CT scans. False-positive 18 F-FDG uptake in the neck was often caused by several sources including muscle, brown fat, salivary glands, vocal cords, tonsils, and other lymphoid tissues. Moreover, reactive hyperplasia lesions, inflammatory lesions and benign tumors can also lead to FDG uptake 24 . All false-positive uptakes were located in the neck, which was similar to what Ozkan et al. reported 16 . Ozkan et al. considered that it was difficult to distinguish recurrent lesions from false-positive lesions using SUV max ≥ 2.5 t in the neck region because of overlapping SUVs between them 16 . Therefore, the criterion for positive lesion was accepted as 18 F-FDG uptake greater than that of the normal surrounding tissue or when the SUV max was ≥ 2.5 in our study.
With respect to distant metastases from included PTC patients, only 4 cases with lung metastases were detected by 18 F-FDG PET/CT scan, all of which showed that PTC patients with negative Tg, negative 131 I-WBS and progressively increased TgAb level weren't prone to distant metastases. It was very possible because distant metastases of DTC produced more serum Tg which couldn't be completely interfere by TgAb 25 . All of them received additional 131 I therapy and showed negative post therapy 131 I-WBS scan results.
Of 23 cases with negative 18 F-FDG PET/CT finding, 10 patients were interpreted as false-negative. Suspicious recurrent lymph node metastases were detected on the neck, which may suggest that negative 18 F-FDG PET/ CT finding may represent a small or well-differentiated metastatic lesions 26 . Subsequently, these patients underwent empirical 131 I therapy using 150 mCi. After 3-5 days, 3 patients with metastatic lesions were detected and confirmed by 131 I-WBS combined with 131 I-SPECT/CT. The remaining 7 patients showed negative 131 I-WBS and recurrent lesions were confirmed pathologically by surgical resection. In the current study, there are also 13 true-negative patients with progressively increased TgAb level, while 7 out of these patients were surgically confirmed as disease free, and the remaining 6 cases were confirmed by follow-up.
With regard to true-negative and false-positive finding in these patients, it was not uncertain whether a few other reasons made serum TgAb rise continuously except for the recurrent diseases of PTC, for that a few other diseases could lead to the increased TgAb, such as type 1 diabetes, rheumatoid arthritis, pernicious anemia,   collagen vascular diseases, scleroderma, chronic urticarial, autoimmune hyperthyroidism and increasing age in healthy women has been reported 22,[27][28][29][30] . In our series, univariate analysis revealed that different TgAb level at diagnosis and span for progressively increased TgAb level was related to the positive 18 F-FDG PET/CT finding. The results showed that the sensitivity, specificity of 18 F-FDG PET/CT when TgAb level ≥ 150 IU/mL at diagnosis and span for progressively increased TgAb level ≥ 3 years were clearly higher than that when TgAb level < 150 IU/mL at diagnosis and span for progressively increased TgAb level 3 years, respectively. In previous studies, a varying prevalence of TgAb value for predicting persistent or recurrent of DTC after total thyroidectomy has been reported. Chung et al. considered a serum TgAb level below 100 U/mL as negative, and found elevated TgAb levels in 22.6% of DTC patients after 131 I ablation 17 . Seo et al. reported that recurrence for DTC was more frequent in patients who showed a persistently elevated TgAb level over 140 U/mL 31 . While other studied have defined TgAb level of 6-100 U/mL as positive 32,33 . In our study, different TgAb levels were used as cutoff values to evaluate the diagnostic performances of 18 F-FDG PET/CT scan in the detection of recurrent PTC. 18 F-FDG PET/CT results could be affected by lesion size, false-positive finding and degree of differentiation of PTC and so on, therefore, above research results for TgAb level may be not related to the positive 18 F-FDG PET/CT finding. Our study also showed that longer span for progressively increased TgAb level (≥3 years) rather than shorter pan for progressively increased TgAb level (<3 years) indicated a higher sensitivity, specificity of 18 F-FDG PET/CT scanning in detecting recurrent PTC, suggesting the recurrent diseases of these PTC patients developed more slowly and have a relatively good prognosis.

F-FDG PET-CT All patients TgAb level at diagnosis (IU/mL) Progressive increase in TgAb level (years)
However, several limitations of this study should be discussed. First, of 13 true negative patients, 6 patients weren't confirmed having metastases by pathology. These cases were classified as true negative through follow-up. In the course of follow-up, these 6 patients showed negative findings on the post-therapy 131 I-WBS, neck US and contrast-enhanced chest CT, 99m Tc-MDP bone scan, but some occult lesions may still not be found. Second, Of 10 false-negative patients, 3 patients were confirmed by 131 I-WBS combined with 131 I-SPCET/CT rather than the results of pathology, because 131 I-SPECT/CT effectively excluded residual noncancerous thyroid tissue located outside the thyroid bed (substernal goiter or ectopic foci along the thyroglossal duct), physiologic uptake in non-thyroidal tissues, and contamination 34,35 . The retrospective nature of the data in the present study may be another limitation.

Conclusions
Our study demonstrated that the 18 F-FDG PET/CT scanning had a good diagnostic performance in the selected PTC patients with negative Tg, negative 131 I-WBS at first postablation and progressively increased TgAb level. Span for progressively increasing TgAb level and TgAb level at diagnosis were closely associated with positive 18 F-FDG PET/CT findings. Therefore, 18 F-FDG PET/CT scanning could be performed routinely for PTC patients with negative Tg, negative 131 I-WBS at first postablation ablation and progressively increased TgAb level, especially for those whose span for progressively increased TgAb level ≥3 years and/or progressively increased TgAb value up to 150 IU/mL.

Patients and Methods
Patients. This retrospective study was approved by our institutional review board. Informed consents have been waived for most patients except for two patients, whose SPECT/CT images were used in the current study. All methods were performed in accordance with the relevant guidelines and regulations. Files of consecutive 7843 patients treated with 131 I between January 2005 and January 2014 were reviewed. Clinical follow-up data of 1257 patients with DTC who underwent 18 F-FDG PET/CT scanning were evaluated retrospectively. The inclusion criteria were as follows: (1) patients with histologically proven PTC. (2) patients with PTC treated with total or near-total thyroidectomy and postoperative 131 I ablation. (3) postablation negative 131 I-WBS defined by the absence of non-physiological 131 I uptake outside the thyroid bed or abnormal 131 I uptake confirmed for physiological uptake or contamination by 131 I single photon emission computed tomography/computed tomography ( 131 I-SPECT/CT) outside the thyroid bed. (4) negative Tg defined as Tg < 0.2 ng/mL (TSH suppression) or Tg < 1 ng/mL (after stimulation) 6 months after the first remnant ablation. (5) progressively increased TgAb level including TgAb which persistently rose or TgAb which kept stable/decreased for some time but subsequently rose after remnant ablation. (6) 18 F-FDG PET/CT was performed more than 1 year after the first remnant ablation. The exclusion criteria were as follows: (1) Tg ≥ 0.2 ng/mL (TSH suppression) or ≥1 ng/mL (after stimulation) in the follow-up. (2) persistently high TgAb but had no rising trend (3) a temporarily increased TgAb at 6-12 months after ablation therapy. 131 I empiric treatment. After surgery, each patient received an ablative dose of 131 I and was put on a low iodine diet for 3-4 weeks before 131 I therapy (TSH reached 30 mIU/L). Subsequently, the patients were subjected to oral administration of 131 I after the following conventional measurements, including FT3, FT4, TSH, Tg, TgAb, neck ultrasonography (US), and CT scans. The dose of oral standard administration of 3.7GBq (100 mCi) of 131 I was used to ablate the thyroid remnants. 131 I-WBS and/or 131 I-SPECT/CT fusion imaging was performed 3-5 days after 131 I oral administration. 131 I-WBS was performed in both anterior and posterior projections using a dual-head SPECT with High-energy collimators and a 364-keV photo peak. 131 I-SPECT/CT images were acquired immediately after planar imaging for PTC patients who presented suspicious finding on 131 I-WBS. 18 F-FDG PET/CT Scan. Patients were instructed to fast for at least 6 hours before the injection of 18 F-FDG.
Blood glucose level was measured before injection and 18 F-FDG was administered at glucose levels < 150 mg/dL. 18 F-FDG PET/CT scanning was performed after an i.v. injection of 3-4MBq/Kg 18 F-FDG, followed by a one hour uptake phase. No intravenous contrast agent was administered. 18 F-FDG PET/CT images were performed using a dedicated GE Discovery PET/CT scanner including 64 slice CT scanners with a dedicated PET (BGO plus crystal). 18 F-FDG images were acquired for 4 minutes at each bed position from the skull base to the superior mediastinum with patients' arms along the chest and from the neck to the mid-thigh with patients' arms above the head. No specific breathing instructions were given. The CT scan was obtained from the orbitomeatal line and progressed to the mid-thigh with the use of a standardized protocol involving 140 kV, 110 mA, 0.8 seconds/ rotation, pitch of 1.75:1, length of scan: 1.0 to 1.6 m, 0.625 spatial resolution, and slice thickness of 3.75 mm. Attenuation correction of PET images was performed using attenuation data from CT and images reconstruction was done using a standard reconstruction algorithm with ordered subset expectation maximization (OSEM). Image fusion was performed using coordinate based fusion software and subsequently reviewed at a workstation (Xeleris) that provided multi-planar reformatted images and displayed PET, CT, and PET/CT fusion images.
Neck US. US were performed on the day of 131 I administration and every 3-6 months after 131 I ablation on a high-resolution ultrasound system equipped with a high-energy 14 MHz linear probe, allowing to work in fundamental B-mode and in power Doppler mode. The thyroid bed, central and lateral neck compartments were included for neck US examination. Suspicion of lymph node metastases of PTC was based on the following criteria: hyperechoic punctuations, cystic appearance, hypervascularization, round shape node without hyperechoic hilum and a short axis greater than 7 mm 36 .
Tg and TgAb measurement. Serum Tg and TgAb levels were measured by electrochemiluminescence immunoassay (ECLIA) methods on the Cobas analyzer (Roche Diagnostics GmbH). The analytical sensitivity was <0.1 μg/L with reference range 1.4-78 μg/L. The analytical sensitivity of TgAb is < 10 IU/mL with a reference range of 10-4000 IU/mL. Follow-up. Serum Tg was performed at TSH suppression or at after TSH suppression 6 months after first remnant ablation. Subsequently, FT3, FT4, TSH, Tg, TgAb at TSH suppression and neck US were measured and performed every 3-6 months in the follow-up of the period, respectively. Progressively increased TgAb levels were measured no less than three times. All 18 F-FDG PET/CT scan were performed at TSH suppression. Contrast-enhanced CT was performed for a few patients after 18 F-FDG PET/CT scan. The last neck US at diagnosis, contrast-enhanced CT and 18 F-FDG PET/CT scan were performed at a maximum interval of less than 30 days. The follow-up period was 2-9 yr with a median follow-up of 5.1 yr. Image analysis. 18 F-FDG PET/CT images were reviewed and interpreted by 2 experienced nuclear medicine physicians (Z-L Qiu and W-J Wei). All 18 F-FDG PET/CT were considered as negative or positive. The criterion for positive lesion was accepted as 18 F-FDG uptake greater than that of the normal surrounding tissue or when the SUV max was ≥ 2.5. The anatomical confirmation with a lesion was detected with matched CT scan. The criterion for negative lesion was that there was no 18 F-FDG uptake and no corresponding identifiable lesion on matched CT scans.
Evaluation of 18 F-FDG PET/CT findings. 18 F-FDG PET/CT results were correlated with surgical and histopathological findings, 131 I-WBS combined with 131 I-SPECT/CT after 131 I treatment once again, other imaging modalities including neck US, chest CT, 99m Tc-MDP bone scan and follow-up. A true-positive finding was confirmed when a lesion was detected as positive by 18 F-FDG PET/CT and the patient was found to have recurrent disease by surgical pathology. A false-positive finding was confirmed when a lesion was excluded by surgical pathology in the patients with positive lesions on 18 F-FDG PET/CT. A false-negative finding was confirmed when a lesion couldn't be detected on 18 F-FDG PET/CT, but it could be found to be recurrent disease by surgical pathology or by 131 I-WBS combined with 131 I-SPECT/CT after 131 I treatment once again. A true-negative finding were confirmed when a lesion was detected as negative by 18 F-FDG PET/CT and the patient was found to have benign disease by surgical pathology or it could be wasn't found to have recurrent disease on other imaging modalities including neck US, chest CT and 131 I-WBS and 99m Tc-MDP bone scan in the follow-up period.
Statistical analysis. Statistical analyses were performed with the SPSS v.17.0 statistical package (SPSS, Inc., Chicago, IL, USA). Descriptive statistics were represented as frequency and percentage. Categorical variables were compared by Pearson Chi-square. The categorical variables for positive 18 F-FDG PET/CT were analyzed by univariate logistic regression. The sensitivity, specificity, positive and negative predictive values, and accuracy of 18 F-FDG PET/CT for the detection of recurrent thyroid cancer were calculated. Together with their 95% confidence intervals (CIs), the odds ratios (OR) for 18 F-FDG PET/CT findings were calculated by univariate logistic regression. A P value of <0.05 was considered to be statistically significant and all reported P values are two-side.