Negative 131I Whole-body Scan Research Articles

Impact of 18F-FDG PET/CT on treatment of patients with differentiated thyroid carcinoma, negative 131I whole body scan and elevated serum thyroglobulin.

Objective(s): 18F-FDG PET/CT is increasingly performed in patients with differen-tiated thyroid cancer. The aim of this study was to assess the clinical impact of 18F-FDG PET/CT on the management of patients with differentiated thyroid carcinoma who had elevated serum thyroglobulin (Tg) and negative 131I whole body scan (WBS). Methods:67 patients with differentiated thyroid carcinoma were included in this study. The findings of 18F-FDG PET/CT imaging were compared with histo-pathology, follow up imaging, or clinical follow-up results. The diagnostic accuracy of 18F-FDG PET/CT was evaluated for the entire patient group and for those patients with stimulated serum thyroglobulin levels of less than 5, 5–10, and more than 10 pmol/L as well as for local recurrences and metastases sites. The impact of 18F-FDG PET/CT on therapeutic management was also evaluated. Results:30/67 patients had positive findings on 18F-FDG PET/CT; 28 were true-positive and 2 were false-positive. 18F-FDG PET/CT results were true-negative in 36 patients and false-negative in 1 patient. The overall sensitivity, specificity, accuracy, PPV and NPV of 18F-FDG PET/CT were, 96.5%, 94.5%, 95.5%, 93.3%, and 97.2% respectively. Positive 18F-FDG PET/CT findings were directly correlated with stimulated serum thyroglobulin levels, 7.1% had Tg between 5–10, and 92.9% had Tg greater than 10 pmol/L. 18F-FDG PET/CT had a high or moderate impact on treatment management in 28 (41.8%) of patients.Conclusion: 18F-FDG PET/CT is able to improve diagnostic accuracy and have management impact in a therapeutically relevant way in patients with differentiated thyroid carcinoma who present with rising thyroglobulin level, negative 131I WBS, and clinical suspicion of recurrent disease.

Value of 18F-FDG Hybrid PET/MR in Differentiated Thyroid Cancer Patients with Negative 131I Whole-Body Scan and Elevated Thyroglobulin Levels.

PurposeTo evaluate the diagnostic performance of 18F-FDG PET/MR in detecting recurrent or metastatic disease in patients with differentiated thyroid cancer (DTC) who have increased thyroglobulin (Tg) levels but a negative 131I whole-body scan (WBS). The relationship between 18F-FDG PET/MR and serum Tg levels was explored. We also evaluated the therapeutic impact of PET/MR on patient clinical management.Patients and MethodsTwenty-nine DTC patients with a negative 131I-WBS of the last post-therapeutic and increased Tg levels under thyroid-stimulating hormone suppression treatment who underwent 18F-FDG PET/MR examination were retrospectively analyzed.ResultsOf those 29 patients, 18F-FDG PET/MR findings were true positive, true negative, false positive, and false negative in 18, 7, 2, and 2 patients, respectively. The overall sensitivity, specificity, and accuracy were 90.0%, 77.8%, and 86.2%, respectively. We noticed significant differences in serum Tg levels between the PET/MR-positive and PET/MR-negative patient groups (P=0.049). Receiver operating characteristic curve analysis showed that a Tg level of 2.4 ng/mL was the optimal cut-off value for predicting PET/MR results. The sensitivity, specificity, and accuracy of PET/MR were higher in patients with Tg levels greater than 2.4 ng/mL than in patients with lower levels. By detecting recurrent or metastatic disease, 18F-FDG PET/MR altered the clinical management in 7 patients (24.1%) of the overall population.Conclusion18F-FDG PET/MR has high diagnostic accuracy for detecting recurrent or metastatic diseases in DTC patients and is useful for clinical management.

Low-dose radioiodine therapy for patients with intermediate- to high-risk differentiated thyroid cancer.

The efficacy of low-dose radioiodine therapy (RIT) for intermediate-risk or high-risk differentiated thyroid cancer (DTC) patients is controversial. Because of the country's shortage of medical facilities for RIT, 1110-MBq RIT for higher risk DTC patients has been performed on an outpatient basis since 2010 in Japan. Herein, we addressed this issue and attempted to determine prognostic factors for the prediction of RIT outcomes. We retrospectively analyzed the cases of 119 patients with papillary thyroid cancer who underwent their first RIT with 1110MBq radioactive iodine (RAI) following a total thyroidectomy, including 65 (54.6%) intermediate-risk and 54 (45.4%) high-risk patients (according to Japan's 2018 clinical practical guidelines for thyroid tumors). Successful ablation was defined when a negative I-131 whole-body scan and thyroglobulin (Tg) < 2ng/mL were obtained at a diagnostic scan performed 148-560days (median 261days) after the first RIT. The overall ablation success rate was 23.4%. Although the ablation success rates of each pretreatment protocol [recombinant human thyroid stimulating hormone and thyroid hormone withdrawal (THW)] did not differ significantly, THW tended to result in a higher success rate than rhTSH. The Tg level at RIT was the only independent powerful predictive factor for successful ablation. The best cut-off value of Tg for predicting unsuccessful ablation was 9ng/mL. The ablation success rate was much lower than those of earlier studies; the most plausible reason would be that higher risk DTC patients were included in this study. The low-dose RIT routinely performed in Japan might be inadequate for the achievement of successful ablation. At least for patients with Tg > 9ng/mL at the first RIT, a higher dose of RAI is recommended.

Clinical Value of 99mTc-3PRGD2 SPECT/CT in Differentiated Thyroid Carcinoma with Negative 131I Whole-Body Scan and Elevated Thyroglobulin Level

The aim of this study was to assess the usefulness of integrin imaging with 99mTc-PEG4-E[PEG4-c(RGDfK)]2 (99mTc-3PRGD2) single photon emission computed tomography (SPECT)/computed tomography (CT) in detecting recurrent disease in patients with differentiated thyroid cancer (DTC), negative radioiodine whole-body scan (WBS) and high serum thyroglobulin (Tg). Thirty-seven patients who underwent total thyroidectomy followed by radioactive iodine ablation and had negative radioiodine WBS but elevated Tg levels were included. 99mTc-3PRGD2 SPECT/CT was performed 1 week after the negative diagnostic 131I WBS. Diagnostic performance indicators, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), for 99mTc-3PRGD2 SPECT/CT was calculated. The correlations between SPECT/CT results and clinic-pathological characteristics were examined. In 30 (81.1%) of the 37 patients, 99mTc-3PRGD2 SPECT/CT showed positive uptake. The sensitivity, specificity, PPV, and NPV of SPECT/CT to detect recurrent disease at follow-up were 96.6%, 75%, 93.3% and 85.7%, respectively. The sensitivity and PPV of SPECT/CT increased with increasing serum Tg levels. 99mTc-3PRGD2 SPECT/CT showed high sensitivity and PPV in the detection of recurrence among DTC patients with higher Tg levels and negative WBS, and the probability of obtaining a positive SPECT/CT result was related with the level of Tg.

Risk factors and stratification for recurrence of patients with differentiated thyroid cancer, elevated thyroglobulin and negative I-131 whole-body scan, by restaging 18F-FDG PET/CT.

In nearly 20%-30% of patients with differentiated thyroid carcinoma (DTC) relapse and 7% of them die during the next 10 years after initial diagnosis. In 10%-30% of patients with DTC after ablation therapy during the follow-up show a negative iodine-131 (131I) whole-body screening test (131I WBS) and increased serum thyroglobulin (Tg) level. Loss of ability of DTC metastatic lesions to trap 131I is associated with pure survival and often aggressive disease. Several studies have shown that in DTC cases non trapping 131I, fluorine-18-fluorodeoxyglucose positron emission tomography (18F-FDG PET) can detect recurrence or metastases with high sensitivity (80%-90%). The purpose of this study was to investigate the clinicopathologic features and other related risk factors of patients with DTC having elevated Tg levels and negative 131I WBS in which recurrence was detected by 18F-FDG PET/CT. We tried to study and stratify patients in this grey zone who could benefit from 18F-FDG PET/CT for the detection of metastases/recurrence according to predefined risk factors not investigated by other researchers. We studied retrospectively 165 DTC patients with elevated Tg levels and a negative 131I WBS during their follow-up between 2004-2015. Metastases/recurrence was found in 49% of the patients on restaging with 18F-FDG PET/CT and were compared with nonmetastatic group according to predefined risk factors. These factors were also evaluated in true positive and false negative cases. The sensitivity and specificity of 18F-FDG PET/CT for detecting recurrent/metastatic disease were 90% and 98.5%, respectively. No apparent predefined risk factor impacting a false negative 18F-FDG PET/CT was found. Findings in follicular carcinoma, Hürtle cell carcinoma and papillary carcinoma were not different from positive PET findings. The variants of papillary carcinoma also had no statistically difference with regard to 18F-FDG results. The most important factors affecting a true positive 18F-FDG PET/CT study were: ETE, high total 131I dose and the SUVmax values over 4.5.

The application of 18F-FDG PET/CT in thyroid tumor

The clinical application of 18F-FDG PET/CT in thyroid tumor is primarily for restaging of patients with DTC but having a negative 131I whole-body scan in the presence of elevated serum Tg and TgAb levels. In parallel with the accumulation of clinical experience and increasing clinical utilization of 18F-FDG PET/CT, the application of 18F-FDG PET/CT in thyroid tumors is also broadened. This review aims at updating the application of 18F-FDG PET/CT in different types of thyroid tumors. Key words: Thyroid neoplasms; Tomography, emission-computed; Tomography, X-ray computed; Deoxyglucose; Trends

Value of Dedicated Head and Neck 18F-FDG PET/CT Protocol in Detecting Recurrent and Metastatic Lesions in Post-surgical Differentiated Thyroid Carcinoma Patients with High Serum Thyroglobulin Level and Negative 131I Whole-body Scan.

Objective(s):In clinical practice, approximately 10-25% of post-surgical differentiated thyroid carcinoma (DTC) patients with high serum thyroglobulin (Tg) and negative 131I whole-body scan (WBS) have poor prognosis due to recurrent or metastatic lesions after radioactive iodine treatment. The purpose of this study was to evaluate the value of 18F-FDG PET/CT scan in DTC patients with high serum Tg level and negative 131I WBS.Methods:69 post-surgical DTC patients with high serum Tg level and negative post ablation 131I WBS were enrolled in this study. All DTC patients underwent head and neck ultrasound, CT scan and whole-body 18F-FDG PET/CT, based on the dedicated head and neck protocol.Results:Overall, 92 lesions were detected in 43 (62.3%) out of 69 patients with positive 18F-FDG PET/CT scan, compared to only 39 lesions detected on CT scan in 26 (37.7%) out of 69 patients. The sensitivity, accuracy and negative predictive value of 18F-FDG PET/CT were 88%, 87% % and 76%, respectively, which were significantly higher than those of CT scan (67.2%, 54.3% and 48.8%, respectively) (P<0.01). Specificity and positive predictive value of 18F-FDG PET/CT (90.5% and 95.2%, respectively) were similar to those of CT scan (95.2% and 96.2%, respectively) (P>0.05). The maximum standardized uptake value (SUVmax) threshold was 4.5 with a good diagnostic value (sensitivity of 92.3% and specificity of 100%). The dedicated head and neck 18F-FDG PET/CT protocol altered the treatment plan in 33 (47.8%) out of 69 DTC patients with high serum Tg level and negative 131I WBS.Conclusion:Dedicated head and neck 18F-FDG PET/CT protocol showed a higher diagnostic value, compared to CT scan and played an important role in detecting recurrent or metastatic lesions in post-surgical DTC patients with high serum Tg level and negative 131I WBS.

IMAGING IN ENDOCRINOLOGY: 2-[18F]-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography in differentiated thyroid carcinoma: clinical indications and controversies in diagnosis and follow-up

In recent years, 2-[(18)F]-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) has emerged as an important tool for the postoperative management of patients with differentiated thyroid cancer (DTC) and it is widely used in selected clinical situations. The most valuable role that FDG-PET/CT plays in clinical practice is that it can be used to obtain prognostic information in patients with increasing thyroglobulin (Tg) levels and negative (131)I whole-body scan post-thyroidectomy and radioiodine (RAI) ablation. FDG-PET/CT may also have a potential role in the initial staging and follow-up of high-risk patients with aggressive histological subtypes, in the identification of patients who are at the highest risk of disease-specific mortality, in the management of patients with RAI-refractory disease, in clinical trials of novel targeted therapies in patients with advanced metastatic disease, and in the evaluation of thyroid nodules with indeterminate fine-needle aspiration for cytology. However, several controversies remain to be resolved, namely: the cutoff value of Tg in the selection of DTC patients for FDG-PET/CT, whether FDG-PET/CT scanning should be performed under thyrotropin stimulation or suppression, and the clinical significance of thyroid FDG-PET/CT incidentalomas. The aim of the present article is to provide an overview of the data about the molecular basis for, clinical indications of, and controversies related to the use of FDG-PET/CT in patients with DTC.

Unusual Adrenal Gland Metastasis in a Patient with Follicular Carcinoma of the Thyroid Evidenced by (18)F-FDG PET/CT and Confirmed by Biopsy.

Follicular thyroid carcinoma (FTC) is a relatively rare form of differentiated thyroid carcinoma, but it is important to recognise that FTC may be very aggressive, may not respond to radioiodine treatment and may cause life-threatening complications [1, 2]. The use of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) has rapidly grown in the latest years in patients with differentiated thyroid carcinoma (DTC) with a negative radio-iodine scan despite clearly elevated levels of thyroglobulin [3]. The biological pattern of DTC, which loses its thyroid-specific iodide-trapping properties and becomes FDG-avid, reflects enhanced aggressiveness and is related to a worse prognosis than FDG-negative tumours [4]. In addition, there is evidence that several factors associated with FDG positivity (tumour size, lymph node metastasis, and glucose transporter expression and differentiation) are related to a poor prognosis in patients with FTC [5]. A 78-year-old woman with a history of FTC came under our observation to undergo an 18F-FDG PET/CT scan for the first time for restaging purpose. Total thyroidectomy had been performed 19 years previously and radio-iodine treatment reached a total activity level of 1.8 Ci (66.6 GBq) over 10 years. The aggressive treatment did not prevent the development of a widespread metastatic disease involving lymph nodes and bones. The most painful bone metastases were treated with external beam radiation therapy, with effective relief of the symptoms. A suppressive therapy with L-thyroxine was started. Thyroglobulin levels were checked yearly, and were relatively high but under control (maximum value, 32.3 ng/ml). However, the thyroglobulin levels suddenly rose up to 117.5 ng/ml 6 months previously. A 131I whole-body scan was requested but the result was negative (Fig. 1). Therefore the patient was referred to our department to undergo an 18FDG-PET/CT scan. Fig. 1 131I whole-body scan images Sixty minutes following intravenous injection of 138 MBq of 18F-FDG, low-dose CT and PET images from the skull base to mid-thigh were acquired using a hybrid Biograph mCT TOF PET/CT scanner (Siemens Medical Solutions, Erlangen,Germany). Images revealed FDG-avid lesions in the sternum (SUVmax 3.5), L1 (SUVmax 8) and in the lower lobe of the right lung (SUVmax 6.3) (Fig. 2a). Moreover, there was evidence of another pathological uptake (SUVmax 7.3) in the left adrenal gland (Fig. 2b-d). The adrenal lesion was surgically removed and pathological examination revealed metastasis from the FTC (Fig. 3). Fig. 2 a Maximum intensity projection (MIP) image; b transaxial PET image; c transaxial CT image; d transaxial fused PET/CT image. Arrows FDG-avid lesions Fig. 3 Haematoxylin and eosin stained section of the surgically removed adrenal lesion The patient was then referred to the clinical oncologist to evaluate possible further therapies. The adrenal gland is a very uncommon site of metastatic spread from thyroid carcinoma. Only a few cases have been reported in the literature, describing adrenal metastases in patients affected by papillary thyroid carcinoma [6–8] or anaplastic thyroid carcinoma [9]. Although a case of iodine-avid adrenal lesion has been described previously [10], to our knowledge, this is the first case report of an adrenal gland metastasis imaged by 18F-FDG PET/CT in a patient affected by FTC with high thyroglobulin levels and negative 131I whole-body scan.

Prospective evaluation of 68Ga-DOTANOC PET-CT in differentiated thyroid cancer patients with raised thyroglobulin and negative 131I-whole body scan: comparison with 18F-FDG PET-CT

The purpose of the study was to evaluate the role of (68)Ga-DOTANOC PET-CT in differentiated thyroid cancer (DTC) patients with negative (131)I-whole body scan (WBS) along with serially increasing serum thyroglobulin (Tg), and compare the same with (18)F-FDG PET-CT. Sixty two DTC patients with serially rising Tg levels and negative (131)I-WBS were prospectively enrolled. All patients underwent (68)Ga-DOTANOC PET-CT and (18)F-FDG PET-CT within an interval of two weeks. PET-CT analysis was done on a per-patient basis, location wise and lesion wise. All PET-CT lesions were divided into four categories-local, nodal, pulmonary and skeletal. Histopathology and/or serial serum Tg level, clinical and imaging follow up (minimum-1 year) were used as a reference standard. Ga-DOTANOC PET-CT demonstrated disease in 40/62 (65 %) patients and (18)F-FDG PET-CT in 45/62 (72 %) patients, with no significant difference on McNemar analysis (p = 0.226). Per-patient sensitivity and specificity of (68)Ga-DOTANOC PET-CT was 78.4 %, 100 %, and for (18)F-FDG PET-CT was 86.3 %, 90.9 %, respectively. Out of 186 lesions detected by both PET-CTs, 121/186 (65 %) lesions were seen on (68)Ga-DOTANOC PET-CT and 168/186 (90.3 %) lesions on (18)F-FDG PET-CT (p < 0.0001). There were 103/186 (55 %) lesions concordant on both. Excellent agreement was noted between (68)Ga-DOTANOC PET-CT and (18)F-FDG PET-CT for detection of local disease (ĸ = 0.92), while moderate agreement was noted for nodal and pulmonary disease (ĸ = 0.67). (68)Ga-DOTANOC PET-CT changed management in 21/62 (34 %) patients and (18)F-FDG PET-CT in 17/62 (27 %) patients. Ga-DOTANOC PET-CT is inferior to (18)F-FDG PET-CT on lesion based but not on patient based analysis for detection of recurrent/residual disease in DTC patients with negative WBS scan and elevated serum Tg levels. It can also help in selection of potential candidates for peptide receptor radionuclide therapy.

Long-Term Follow-Up of Patients With Differentiated Thyroid Cancer Who had Negative 131I Whole-Body Scan at First Evaluation After Treatment

The evaluation of patients with differentiated thyroid cancer is commonly based on serum thyroglobulin (Tg) measurement and 131I whole-body scan (WBS). The first follow-up (6-12 months after initial treatment) shows the response to therapy, a prognostic factor.The aims of the study were to describe the clinical outcome during a long-term follow-up of patients with negative 131I WBS in the first evaluation, and to assess clinical and histological characteristics related to the outcome in this patient population. This retrospective study reviewed data from 209 patients followed at 2 Brazilian hospitals. A minimum of 10 years of follow-up was required. During mean follow-up of 13.7 ± 4.2 years, 20% of patients developed recurrence. At the end of follow-up, 21% of patients had persistent disease. The clinical and histological characteristics related to adverse outcomes (recurrence or persistent disease) were lymph node metastases at diagnosis, high risk according to American Thyroid Association (ATA) classification, and incomplete response to treatment. Stimulated Tg levels (under thyroid hormone withdrawal) and basal Tg levels (with thyroid hormone) greater than 10 ng/mL at first evaluation were associated with an adverse outcome. Negative WBS at first evaluation should not be used as an isolated prognostic factor. This must be considered together with histopathological (ATA classification, lymph node metastases) and clinical/laboratory characteristics (stimulated and basal Tg; response to therapy).

Correlation of 18F-FDG PET/CT Findings With Histopathological Results in Differentiated Thyroid Cancer Patients Who Have Increased Thyroglobulin or Antithyroglobulin Antibody Levels and Negative 131I Whole-Body Scan Results

This study aimed to investigate the correlation of 18F-FDG PET/CT findings with histopathological results in defining the recurrence of the disease in patients with differentiated thyroid cancer (DTC) who have increased thyroglobuline (Tg) or anti-Tg antibody (TgAb) levels and negative 131I whole-body scan (WBS) result. A total of 59 patients with DTC (44 women, 15 men; mean [SD] age, 48.2 [22.6] years) were included in the study. All of the patients had previous papillary thyroid cancer, and all of them had undergone radioiodine ablation after a total or near-total thyroidectomy. After radioiodine ablation, patients were followed up for approximately 2.5 years. In the follow-up, the patients with negative 131I-WBS results and increased Tg or TgAb levels under thyroid-stimulating hormone-stimulated conditions underwent an 18F-FDG PET/CT scan to determine any recurrence of disease. There were negative or uncertain findings in the neck ultrasonography and/or thorax CT in most of the patients. The 18F-FDG PET/CT findings were compared with the histopathological results in all patients. Although 49 patients had increased Tg levels, the remaining 10 patients had increased TgAb levels. In patients with high Tg levels, 18F-FDG PET/CT scan results were negative in 10 and positive in 39 patients. In this patient group, 18F-FDG PET/CT findings were true positive, true negative, false positive, and false negative in 32, 3, 7, and 7 patients, respectively. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 18F-FDG PET/CT in this group were calculated as 82%, 30%, 80%, 30%, and 71%, separately. In the receiver operating characteristic analysis, a 4.5 cutoff SUV(max) was calculated with 75% sensitivity and 70% specificity for predicting disease recurrence. Cutoff Tg level was calculated as 20.7 ng/mL with 75% sensitivity and 55% specificity. In 10 patients with high TgAb levels, 18F-FDG PET/CT was true positive, true negative and false positive in 6, 2, and 2 patients, respectively. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 18F-FDG PET/CT in this patient group were calculated as 100%, 50%, 75%, 100%, and 80%, respectively. 18F-FDG PET/CT may be a useful imaging modality in defining recurrence of the disease in patients with DTC who have increased Tg or TgAb levels, negative 131I-WBS results, and negative or suspicious neck ultrasonography and/or thorax CT results. Although 18F-FDG PET/CT seems to be a more sensitive method in patients with increased TgAb levels, the number of patients is not enough to make a substantiated comment.

Prognostic Significance of FDG PET/CT on the Follow-up of Patients of Differentiated Thyroid Carcinoma With Negative I131 Whole-Body Scan and Elevated Thyroglobulin Levels

Department of Nuclear Medicine Department Fondazione Poliambulanza Brescia, Italy [email protected] Conflicts of interest and sources of funding: none declared.

A randomized equivalence trial to determine the optimum dose of iodine-131 for remnant ablation in differentiated thyroid cancer

We conducted a stratified randomized equivalence/noninferiority trial from January 2001 to December 2006 to determine whether lower administered activities are as effective as 3.7 GBq (100 mCi) of iodine-131 (I) for remnant ablation. The sample size was found to be 450 on the basis of 80% power (α=5%) and noninferiority margin (δ=0.15). We used an allocation ratio of 2 : 2 : 1 for the 0.93, 1.85, and 3.7 GBq (25, 50, and 100 mCi) groups, respectively. Randomization with concealment was followed for patient group allocation. All patients underwent preablation I whole-body scan, 48-h radioiodine neck uptake measurements and post-therapeutic scans. The patients were advised suppressive L-thyroxine therapy (2 µg/kg/day). Repeat evaluation was performed after 6 months, along with thyroglobulin and antibody assays. The criteria for ablation were as follows: major criterion - negative I whole-body scan; minor criteria - 48-h radioiodine neck uptake less than or equal to 0.2% and stimulated thyroglobulin less than or equal to 10 ng/ml. A total of 422 patients who fulfilled the inclusion criteria (360 papillary and 62 follicular) could be recruited. As per AJCC, 6th ed., we had 70, 11, and 19% of patients in stage I, II, and III, respectively. First-dose ablation was 81.5, 84.9, 88.5, and 84.2% in the 0.93, 1.85, and 3.7 GBq groups and overall, respectively. Histology had no effect on ablation rate. The equivalence testing of the hypothesis was conducted between the 0.93 and 3.7 GBq groups, the 1.85 and 3.7 GBq groups, and the 0.93 and 1.85 GBq groups. Results showed that, at a significance level of 5%, the null hypothesis was rejected for each pair. First-dose I ablation rates at 6 months with 0.93, 1.85, and 3.7 GBq of I are equivalent with the prespecified clinically acceptable noninferiority margin. We conclude that we are probably administering too much I for remnant ablation (trial registration number: CTRI/002291).

Prognostic Significance of FDG PET/CT on the Follow-Up of Patients of Differentiated Thyroid Carcinoma With Negative 131I Whole-Body Scan and Elevated Thyroglobulin Levels

This study aimed (a) to determine the clinical and histopathologic factors that are related to FDG avidity in the recurrence/metastases of patients with differentiated thyroid carcinoma (DTC) who present with elevated thyroglobulin (Tg) levels and negative 131I whole-body scans (WBSs), (b) to clarify Tg cutoff levels in this setting, and (c) to evaluate the impact of PET/CT on patient management strategies and hence to critically look into the importance of PET/CT in combination with Tg in clinical decision making. A total of 105 patients with DTC with negative 131I WBS and neck ultrasound but elevated Tg, who underwent FDG PET/CT for the suspicion of recurrent/metastatic disease, were included in this analysis. All patients had previously undergone total thyroidectomy and radioiodine ablation/therapy. PET/CT results were correlated with Tg levels and clinical and histopathologic characteristics of the primary tumor compared with the follow-up data. PET/CT was true-positive in 69 patients (of which 23 had surgically amenable disease), true-negative in 20, false-positive in 6 patients and false-negative in 10 patients. Extrathyroidal spread was an independent risk factor related to FDG-avid recurrence. Tumor size was significantly higher in PET-positive patients than others, 2.25 (1.8) versus 1.5 (1.1) cm, P = 0.02. Significant correlation was observed between PET positivity and high Tg levels (P = 0.0001). Receiver operating characteristic curve analysis demonstrated a Tg cutoff of 1.9 ng/mL under thyroid-stimulating hormone suppression, 38.2 ng/mL with thyroid-stimulating hormone stimulation. Among PET-negative patients, no recurrence was detected in patients with undetectable/suppressible Tg in on-therapy state. PET positivity correlated with extrathyroidal spread, and elevated Tg in recurrent/metastatic DTC. FDG PET/CT in combination with Tg levels was crucial in defining management strategies in patients with DTC with negative 131I WBS. A negative FDG PET/CT scan predicts a favorable prognosis and lack of recurrence on follow-up in patients with "suppressible Tg" levels in the on-therapy state despite significant elevation of Tg in the off-therapy state.

Role of 18F-FDG - PET/CT in Patients with Differentiated Thyroid Cancer Who Present with Elevated Thyroglobulin and Negative 131I Whole Body Scan

Aim of the work: To detect the ability of 18F-FDG with PET/CT to explain the elevated Tg levels in patients with negative 131I whole body diagnostic dose scan and to correlate of 18F-FDG with PET/CT with other diagnostic methods and histopathologic diagnosis.Patients and methods: 20 patients (13 males and 7 females) with pathologicall proven differentiated cancer thyroid were included in the study. All patients were subjected to near total thyroidectomy. 8 out of the 20 patients also underwent lymph node dissection. All received 131I ablation and had a negative whole body scan during follow up. They had unexplained elevated (> 10 ng/ml or more) or rising serum Tg levels (5-10ng/ml). All patients were subjected to full history, clinical examination, Laboratory and radiological assessment as well as 18F-FDG PET/CT study.Results: Neck US detected 7 lesions in 6 patients, all of them confirmed to be positive by PET/CT and an additional 13 neck lesions were detected by PET/CT in 15 patients. CT chest detected 8 patients, 6 of them confirmed by PET/CT while 2 lung lesions were negative. Eight additional mediastinal lymph node metastases were detected by PET/CT. PET/CT showed positive findings in 19/20 patients. In the remaining no cause for the elevated Tg was found with PET/CT or other radiological methods. PET/CT directed the management in 14/20 patients either to surgery or to external radiotherapy with normalization of Tg level within weeks after treatment.Conclusion: 18F-FDG PET/CT is of undeniable clinical value in patients with negative 131I whole-body scan results who are suspected of having a metastatic thyroid disease. It is able to detect significantly additional tumor sites than US or CT procedures.

Detection of Subcentimeter Metastatic Cervical Lymph Node by 18F-FDG PET/CT in Patients With Well-Differentiated Thyroid Carcinoma and High Serum Thyroglobulin But Negative 131I Whole-Body Scan

This study aimed to evaluate the diagnostic value of 18F-FDG PET/CT and identify the best parameter to detect subcentimeter cervical nodal metastasis in patients with a well-differentiated thyroid carcinoma (WDTC), elevated serum thyroglobulin (Tg) levels, but negative findings in the 131I whole-body scan (WBS). We prospectively studied 30 consecutive patients with WDTC after standard surgery and radioiodine treatment. All patients had serum Tg greater than 10 ng/mL during thyroid hormone withdrawal but negative findings in the therapeutic 131I WBS. One whole-body CT scan and serial whole-body and neck PET scans were performed between 10 and 170 minutes after 18F-FDG injection. Parameters studied were SUVmax, percent change in SUVmax, SUV ratios of lesions to reference organs, and their percent change. Result in the PET/CT scan was correlated with histopathology and follow-up information. Patient-based and lesion-based (subcentimeter cervical lymph nodes) analyses were performed. Outcome of Tg level after lymph node resection was also analyzed. The overall sensitivity, specificity, accuracy, and positive and negative predictive values were 100%, 78%, 93%, 91%, and 100%, respectively. In lesion-based analysis, the differential SUVmax between 2 time points did not provide higher sensitivity than the individual SUVmax at the 60th or 90th minute. A combined SUVmax at the 90th minute greater than 2.75 and a percent change of SUVmax between the 60th and 90th minute greater than -1.1% provides the best diagnostic value with sensitivity, specificity, accuracy, and positive and negative predictive values of 81%, 90%, 83%, 97%, and 56%, respectively. After surgery, patients with completely resected PET-positive nodes without distant metastasis showed reduction of suppressed Tg to less than 2 ng/mL. Combined SUVmax at the 90th minute and the percent change of SUVmax between the 60th and 90th minute provides the best diagnostic value to differentiate benign from malignant conditions in subcentimeter lymph nodes.

The influence of I-131 therapy on FDG uptake in differentiated thyroid cancer

18F-fluorodeoxyglucose positron emission tomography (FDG-PET) [or PET/computed tomography (CT)] is more likely to show false-negative results when it is performed shortly after chemotherapy and/or radiotherapy because of "metabolic stunning". The present study aimed to evaluate the influence of I-131 therapy on FDG uptake and the detection of recurrence or metastasis of differentiated thyroid cancer (DTC). We retrospectively enrolled 16 consecutive FDG-PET/CT studies which had been performed in patients with DTC with elevated thyroglobulin (TG) but negative I-131 whole-body scan. All studies were performed under L: -thyroxine suppression. The patients were divided into groups A and B for PET/CT performed within 4 months of I-131 therapy or no such therapy, respectively. Each lesion identified on PET/CT was characterized using a 5-point scale by visual analysis: 0 = definitely benign, 1 = probably benign, 2 = equivocal, 3 = probably malignant, and 4 = definitely malignant. The maximum standardized uptake value (SUV max) in each lesion was also measured for semiquantitative analysis. We compared the visual grading and SUV max of the lesion of highest FDG uptake between groups A and B. For visual analysis, group B had significantly more patients with an uptake score of 3 or 4 than group A (80% vs. 17%, P = 0.01). In addition, there were significantly more equivocal results from group A than from group B (67% vs. 10%, P = 0.02). If the patients with the highest uptake scores of 2, 3, and 4 were considered to be positive for local recurrence or metastasis, there would be no significant difference between the positive rates of groups A and B (83% vs. 90%, P = 0.7). However, the mean SUV max of positive results was significantly lower for group A than for group B (3.1 +/- 0.9 and 6.6 +/- 3.5, respectively, P = 0.02). The preliminary results suggested that FDG uptake in DTC may be negatively influenced by I-131 therapy within 4 months, resulting in lower FDG uptake and more equivocal results. Further studies are necessary to determine whether it is secondary to "metabolic stunning" caused by I-131 therapy.

Therapeutic impact of 18FDG-PET/CT in the management of iodine-negative recurrence of differentiated thyroid carcinoma

18-F-fluoro-2-deoxyglucose positron emission tomography ((18)FDG-PET) is useful in the detection of iodine-negative differentiated thyroid carcinoma (DTC). The aim of this prospective study was to assess therapeutic impact of (18)FDG-PET imaging using a PET/computed tomography (CT) system in patients with iodine-negative recurrence of DTC. From 2002 to 2006, patients with recurrence of DTC diagnosed by elevated thyroglobulin level and negative 131-I whole-body scan were included. Forty-five patients (31 women, 14 men), with a mean age of 55 years, with 36 papillary, 5 follicular, and 4 Hürthle carcinomas, were studied. All patients had previously undergone total thyroidectomy and postoperative thyroid remnant ablation with 131-I. The findings of (18)FDG-PET/CT were positive in 31 patients (68.8%) and negative in 14 (32.2%). Results were true positive in 24 of 31 patients. The sensitivity, positive predictive value, and accuracy of (18)FDG-PET/CT were 63%, 77%, and 53%, respectively. Twenty patients were operated on, 19 had neck surgery with mediastinal lymph node dissection (1 case) and lung resection (1 case), and 1 underwent lung resection. Seven patients had a stimulated thyroglobulin level <1 ng/mL. (18)FDG-PET/CT is able to select patients who can benefit from surgery. Normalization of thyroglobulin is observed in one third of operated patients.

Eficacia diagnóstica de la PET 18F-FDG en el cáncer diferenciado de tiroides residual o recurrente con tiroglobulina elevada y rastreo con 131-I negativo

Introduction 18F-FDG PET has demonstrated its usefulness in detecting recurrences of differentiated thyroid cancer (DTC) with high thyroglobulin (Tg) levels and negative 131I whole-body scan (WBS); however, the number of patients analyzed is low and different studies report disparate results. Objective To estimate the diagnostic accuracy of 18F-FDG PET in this subgroup of patients. Materials and methods Fifty eight patients (64 18F-FDG PET studies) with histologically proven DTC treated with total thyroidectomy followed by at least one session of 131I therapy for the ablation of thyroid remnants were retrospectively analyzed. Results were verified by pathology, clinical follow-up, response to treatment, or by comparison with conventional diagnostic methods. Sensitivity (Se), specificity (Sp), likelihood ratios (LR), diagnostic accuracy (DA), positive and negative predictive values (PPV, NPV), and Tg levels were calculated for patients with positive and negative 18F-FDG PET results. Results Twenty seven studies were true positives, 1 false positive, 25 true negatives, and 11 false negatives. Se was 71 %, Sp 96 %, PPV 96.4 %; NPV 69.4 %, DA 81.3 %, positive LR 17.75, and negative LR 0.3. The mean Tg level was 202.34 ng/ml in patients with positive 18F-FDG PET and 40.94 ng/ml in those with negative 18F-FDG PET; the difference between the two groups (161.4 ng/ml) was significant at p <0.05. Conclusions 18F-FDG PET is a useful for detecting residual or recurrent DTC in patients with elevated Tg and negative 131I WBS.