Nuclear Medicine Review 2/2016-99mTc-EDDA/HYNIC-TOC in the diagnosis of differentiated thyroid carcinoma refractory to radioiodine treatment

99mTc-EDDA/HYNIC-TOC in the diagnosis of differentiated thyroid carcinoma refractory to radioiodine treatment

Rafał Czepczynski, Maria Gryczyńska, Marek Ruchała

Department of Endocrinology and Metabolism, Poznan University of Medical Sciences, Poznań, Poland

 

[Received 30 VI 2016; Accepted 5 VII 2016]

Abstract

BACKGROUND: In majority of cases of differentiated thyroid carcinoma (DTC), the ablative radioiodine treatment shows high efficacy. In a small number of patients, mechanism of selective iodine uptake by the DTC cells is insufficient and alternative methods of diagnosis and treatment are needed. As demonstrated in vitro, DTC cells show expression of somatostatin receptors. Radiolabeled somatostatin analogs are widely used in the diagnosis of neuroendocrine tumors. The aim of the study was to evaluate the utility of peptide receptor scintigraphy with the use of 99mTc-EDDA/HYNIC-TOC in the diagnosis of DTC in patients with elevated thyroglobulin concentrations (Tg), negative WBS and no effect of the consecutive radioiodine therapies.

MATERIAL AND METHODS: Whole body scintigraphy as well as SPECT of neck and chest were performed 3 and 24 h after i.v. administration of 740 MBq 99mTc-EDDA/HYNIC-TOC. The obtained images were compared with other radionuclide and radiological imaging methods. Forty-three patients with DTC after surgery and ablative radioiodine treatment with negative WBS and elevated Tg were qualified. Patients’ age: 18-83 years (mean 58.0).

RESULTS: SRS showed foci of tracer accumulation in 29 cases (67.4%). Sensitivity was 69.0% specificity 78.6%. SRS correctly identified local recurrence in 8 pts., metastatic lymph nodes in 19 pts., lung metastases in 12 pts. and bone metastases in 5 pts. SRS showed high sensitivity in the detection of metastatic lymph nodes (100%) and bone metastases (83.3%) and lung metastases (63.2%). Positive SRS was found in pts. with higher Tg concentrations (130 ± 144 vs. 30 ± 54 ng/ml).

CONCLUSION: Scintigraphy with the use of the studied technetium-99m-labeled somatostatin analog is useful in the evaluation of patients with advanced DTC. It shows relatively good sensitivity and specificity but not high enough to be recommended as a routine imaging method. The role of somatostatin receptor scintigraphy in DTC is complementary to other imaging modalities.

 

KEY words: somatostatin analogs, thyroid carcinoma, scintigraphy

 

Nucl Med Rev 2016; 19, 2: 67-73

Background

Prognosis in differentiated thyroid carcinoma (DTC) is generally good. In less than 20% of patients local recurrence and cervical lymph node metastases may occur after thyroidectomy and radioiodine therapy (RIT). Distant metastases are found in 5-10% of patients; they are located mainly in lungs (57%) and bones (24%) [1]. About 10-15% of patients with DTC have recurrent disease and 25-50% of patients with locally advanced or metastatic DTC become radioactive iodine (1311) (RAI)-refractory [2, 3].

Treatment efficacy is monitored by the measurement of thyroglobulin concentration (Tg). In case of elevated Tg RIT treatment is performed followed by the whole body scan (WBS) that is aimed at the identification of iodine-avid foci of DTC [4], in about 30% of cases DTC cells lose the ability to concentrate iodine [3], it is caused by the dedifferentiation of these cells and mutation of natrium-iodide symporter (NIS) gene that is responsible for the uptake of iodide ions into thyroid cells [5-8], in the situation of elevated Tg and negative WBS other imaging modalities are warranted to detect the localization of DTC foci and evaluate possibility of other treatment options including surgery.

For many years PET-CT using 18fluoro-deoxyglucose (18F-FDG) has been successfully used in the detection of non-iodine avid DTC recurrence [9, 10]. Sensitivity of PET-CT in population of DTC patients with elevated Tg and negative WBS is estimated between 69 and 95%, especially when performed in the conditions of TSH stimulation [11-16], it is especially useful in patients with Tg concentrations above 10 mg/l [17].

Another proposed method to visualize non-iodine avid DTC foci is the somatostatin receptor scintigraphy (SRS). In the first publication on this issue, 4 DTC patients were reported in whom 111-indium labeled octreotide (Octreoscan) was used. The scan was positive in three of these cases [18]. In numerous later studies different percentage of positive scans was reported ranging from 30 to 100% [19-24].

Synthesis of new 99mTc-labeled somatostatin analog that had been carried out at the beginning of this century opened a new era of imaging. 99mTc-labeled compounds showed better diagnostic parameters associated with the preferable physical properties of 99m-technetium in comparison to 111-indium [25-28]. The somatostatin analog, 99mTc-EDDA/HYNIC-TOC (Tektrotyd) showed good diagnostic performance in neuroendocrine tumors [29, 30], in medullary thyroid carcinoma [31] and some other tumors that express somatostatin receptors. The aim of our study was to evaluate diagnostic performance of 99mTc-EDDA/HYNIC-TOC in the diagnosis of DTC refractory to radioiodine therapy.

Material and methods

Material

Patients with suspected dedifferentiation of DTC who presented with elevated Tg and negative WBS were qualified to somatostatin receptor scintigraphy using 99mTc-EDDA/HYNIC-TOC. All patients had undergone total thyroidectomy and at least three courses of RIT. In concordance with local and European guidelines of DTC management [32, 33], the first RIT activity was 60-90 mCi (2.2-3.3 GBq) depending on the risk factors. As none of the qualified patients achieved complete remission, the courses of RIT were repeated with higher 131I activities, ranging from 90 to 150 mCl (3.3-5.5 GBq). The intervals between subsequent courses of RIT ranged from 6 to 12 months. RIT was performed in the conditions of endogenous TSH stimulation after withdrawal of L-thyroxin for at least 4 weeks. Between the courses of RIT, patients were treated with suppressive doses of L-thyroxin (TSH below 0.3 mU/dl). SRS was performed during L-thyroxin treatment, at least 6 weeks after recent RIT.

The control group consisted of patients after total thyroidectomy due to medullary thyroid carcinoma who had SRS for the detection of recurrent disease but who were eventually classified as complete remission, based on the normal values of calcitonin and negative imaging at 2-years follow-up. The obtained SRS were retrospectively utilized as the “normal” image in subjects after thyroidectomy.

Methods

SRS was performed with the use of 99mTc-EDDA/HYNIC-TOC (Tektrotyd) manufactured by Polatom (Poland). The labeling with 99mTc obtained from Mo/Tc generator (Amersham Health) was performed on-site in concordance with the manufacturer’s recommendations (30 min incubation 80°C). The radiochemical purity was assessed with two methods: reverse-phase chromatography and thin-layer chromatography and it ranged between 94.9 and 98.1%.

Each patient was given an i.v. injection of 20-25 mCi (740-925 MBq) of 99mTc-EDDA/HYNIC-TOC. No adverse effects was observed after injection, including allergic reactions.

Images were registered twice in each patient: 3 h and 24 h post injection. Image acquisition was performed using one of the dual-head gamma cameras: Varicam (Elscint, Israel) or Infinia Hawkeye 4 (GE Healtchcare, USA), equipped with low energy – all-purpose collimators. Acquisition parameters were equal for both scanners. Each imaging session consisted of planar whole body scans in anterior and posterior projections (bed movement speed 15 cm/min, 256 x 1024 matrix) and SPECT images of the neck and chest (60 projections, acquisition time 20 s per frame). In patients scanned with Infinia Hawkeye 4 gamma camera, computed tomography for anatomical correlation were also acquired.

Images were interpreted by two experienced nuclear medicine specialists. Foci of increased tracer accumulation were reported, especially in the most probable location of DTC recurrence (thyroid bed, cervical lymph nodes, mediastinum, lungs and bones). The obtained images were compared with other imaging methods used for verification of the findings: cervical ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MR) performed not earlier than 3 months before and not later than 3 months after SRS.

WBS used for the qualification of the patients to the study was performed using the same gamma cameras with the use of high-energy collimators. The WBS was registered 7-10 days after RIT with the use of 90-150 mCi (3.3-5.5 GBq). Negative WBS defined as no indication of pathologic iodine uptake attributed to remnant thyroid tissue of DTC recurrence or metastasis was used as a qualifying criterion in this study.

Tg measurement was performed with the use of radioimmune assay Dynotest Tg-S (Brahms Diagnostics Berlin, Germany) under conditions of endogenous TSH stimulation. Tg concentration above 2 ng/ml was regarded as elevated and considered as the second qualifying criterion in the study.

Results

Forty-three (36 female and 7 male) patients were retrospectively analyzed. The diagnosis of DTC was made 3 to 17 years (median 7 years) before SRS and was based on the histopathological evaluation of the resected thyroid tumor. Histopathological types of DTC were distributed as follows: papillary carcinoma in 25 patients (58.1%), including 2 patients with follicular variant of papillary carcinoma, follicular carcinoma in 11 subjects (25.6%), including one patient with insular carcinoma and oxyphilic carcinoma in 7 patients (16.3%).

Patients’ age ranged from 18 to 83 years (mean 58.0 ± 15.9, median 60 years).

The T stage in TNM classification at the diagnosis was: T1 in 4 patients (15.3%), T2 in 9 pts. (34.6%), T3 in 2 pts. (7.7%) and T4 in 13 pts. (50.0%).

The N stage was estimated as NO in 17 pts. (65.4%) and N1 in 9 pts. (34.6%). In the remaining 17 subjects TNM classification was not available, particularly in patients who were operated on before 2000 outside large surgical centers.

Stimulated Tg concentrations ranged from 0.57 to 523.9 ng/ml (median 38 ng/ml). Two patients with Tg below 2 ng/ml were exceptionally qualified to the study due to highly elevated anti-Tg antibodies (aTg) suggesting a persistent disease despite normal Tg level.

Prior to SRS, the patients had undergone from 3 to 9 courses of RIT with the cumulative activity of 300 to 1440 mCi (11.1 -53.2 GBq), median 720 mCi (26.6 GBq).

SRS showed pathological foci of 99mTc-EDDA/HYNIC-TOC accumulation in 29 patients (67.4%). SRS was negative in the remaining 14 patients (32.6%).

Comparison of the subgroups of patients with positive and negative SRS is presented in Table 1. In the subgroup with positive SRS mean Tg was higher than in the subgroup with negative SRS (p = 0.0164). In patients with oxyphilic carcinoma, SRS was more frequently positive than in other histopathological diagnoses. No difference was noted between the subgroups with respect to patients’ age, time from diagnosis and RIT cumulative activity.

Table 1. Patients characteristics and comparison of selected parameters in the subgroup with positive and negative SRS

  All patients Patients with positive SRS Patients with negative SRS p
n 43 29 14  
Age (years) 58.0 ± 15.9 60.2 ± 16.0 53.9 ± 18.0 0.2078
median 60 61.5 57  
Time from diagnosis (years) LO +l co 8.3 ± 5.1 7.8 ± 7.0 0.7914
median 7 6.5 7  
Cumulative 131I activity [mCi] 653 ± 293 702 ± 274 562 ± 265 0.1203
median 570 690 390  
Tg [ng/dl] 95 ± 127 130 ± 144 30 ± 54 0.0164
median 38 101 8  
Papillary thyroid carcinoma 25 16 9 0.0838
  58.1% 64.0% 36.0%  
Follicular thyroid carcinoma 11 6 5 0.5758
  25.6% 54.5% 45.4%  
Oxyphilic type 7 6 1 0.0001
  16.3% 85.7% 14.3%  

Local recurrence

Pathologic foci in the neck region were found in 16 pts. (37.2%). In 8 of them (18.6%) the lesion was located in the thyroid bed and was interpreted as local recurrence (Figure 1). In 7 cases local recurrence was confirmed using US and biopsy. The patients were referred to further surgical treatment. In one patient the lesion was not found with US but it disappeared after next two courses of RIT performed despite negative WBS.

Figure 1. 62-year-old male patient with oxyphilic carcinoma. SRS detected local recurrence and metastatic supraclavicular lymph nodes on the left side

Lymph node metastases

In 11 patients (25.6%) pathologic foci in the neck outside thyroid bed were found in SRS: in the submandibular region (3 cases) in the posterior neck triangle (2 cases) and in the supraclavicular region (8 cases). In 10 cases these findings were positively verified using US and/or CT and in 8 cases metastatic character of the lesions was confirmed in fine-needle biopsy. The size of the metastatic lymph nodes varied from 7 to 24 mm.

Focal mediastinal uptake was found in 13 patients (27.9%). In one of them the focus was noted only in SPECT image (not in the planar scan). Contrast-enhanced CT revealed pathologic lymph nodes in the areas indicated at the SRS in 9 of these cases. In 2 patients the focus was verified as hypertrophic thymus. In 2 patients the CT did not disclose any pathologic finding in mediastinum, so the SRS was interpreted as false positive.

Distant metastases

In 13 patients (30.2%) focal uptake in the lungs was found: in 3 cases in form of a solitary focus, in 10 cases as multiple lesions. CT confirmed metastatic character of these findings in 12 patients. In 9 of them the metastases were greater than 10 mm. In the remaining case, the lesion had morphology of primary pulmonary malignancy and was finally diagnosed as pulmonary adenocarcinoma.

In 7 patients without pulmonary lesions at SRS, pulmonary metastases with the diameter of 2-6 mm were visualized at CT. In these cases SRS was interpreted as false negative.

In general, pulmonary metastases were present in 19 patients (44.2%). SRS was true positive in 12 of them (Figure 2). Remaining data is presented in Table 2.

Figure 2. Pulmonary and bone metastases (skull, pubic bone, right femoral bone) in a patient with Tg = 523 ng/ml

Table 2. Comparison of different parameters in patients with different findings (mean ± standard deviation and median are presented)

  n Age (years) Papillary carcinoma (n, %) Tg [ng/ml] Time since diagnosis (years) Cumulative radioiodine activity [mCi]
All patients 43 58.0 ± 15.9 25 95 ± 127 8.1 ± 5.1 653 ± 293
    60 58.1% 38 7 570
Pts. with local recurrence 8 46.4 ± 17.9 5 37.4 ± 37.8 7.7 ± 2.1 737 ± 243
    47* 62.5% 19 ♦ 7 630
Pts. with cervical lymph nodes mets 11 63.6 ± 15.4 8 86.6 ± 60.6 7.3 ± 7.1 611 ± 339
    68* 72.7% 95 ♦♦ 7 450
Pts. with mediastinal lymph node mets 12 68.6 ± 9.42 5 132 ± 139 7.4 ± 5.7 648 ± 258
    67** 41.7% 105 6 585
Pts. with pulmonary mets. 20 64.6 ± 15.7 11 105 ± 126 5.9 ± 3.6 699 ± 336
    63*** 55.0% 78 6 600
Pts. with bone mets 6 68.7 ± 10.1 2 227 ± 199 6.7 ± 7.3 673 ± 260
    69**** 33.3% 142 3 630

*p = 0.0382; **p = 0.0019; ***p = 0.013; ****p = 0.0184; ♦p = 0.0205; ♦♦p = 0.0439

Bone metastases were detected in 6 patients (14.0%). Five of them were positive at SRS. The lesions were found in the skull (2 pts.), spine (3 pts.), ribs (2 pts.) and pelvis (1 patient). All these lesions were confirmed by bone scintigraphy, MR and/or PET-CT. In one case, the metastases were found in bone scintigraphy and MR, but not in SRS (false negative scan) (Figure 3). Follicular carcinoma was predominant diagnosis in patients with bone metastases (4 out of 6 cases).

Figure 3. 60-year-old male patient. Mediastinal and hilar lymph node metastases was detected in SRS performed 24 h p.i. (left). The bone scan revealed additionally metastases in the right pelvic bone (right) that were not seen at SRS (false negative finding of bone metastases)

In one patient a previously unknown cerebellar metastasis was detected by SRS in a patient with multiple pulmonary metastases.

In the statistical analysis of the entire group, the mean age was lower among patients with local recurrence in comparison with lymph node or distant metastases. Patients with bone metastases had significantly higher Tg levels than patients with other DTC locations. Complete data is presented in Table 2.

SRS diagnostic performance

Number of positive and negative SRS in general and with respect to different lesion locations is presented in Table 3. For the calculation of diagnostic performance parameters, control group was included in the table.

Table 3. Diagnostic performance of SRS in the studied group

  (1)
SRS
(2)
Patients with DTC
(3)
Control group
(4)
Local recurrence
(5)
Lymph node metastases
(6)
Pulmonary metastases
(7)
Bone metastases
n 56 43 13 8 19 19 6
True positive 29 29 0 8 19 12 5
True negative 11 0 11 48 34 36 50
False positive 3 1 2 0 3 1 0
False negative 13 13 0 0 0 7 1

Based on the presented data, following parameters of the studied SRS with the use of 99mTc-EDDA/HYNIC-TOC were calculated: sensitivity 69.0%, specificity 78.5%, positive predictive value 90.6%, and negative predictive value 45.8%. With respect to the histopathologic type of the disease, sensitivity and specificity were as follows: in papillary thyroid carcinoma sensitivity – 64.0%, specificity – 78.6%; in follicular carcinoma 54.5% and 84.6%; in oxyphilic carcinoma 85.7% and 84.6% respectively.

Discussion

Somatostatin receptors are expressed in both in normal and malignant cells of the neuroendocrine origin [34]. The somatostatin analog labeled with 99m-technetium, 99mTc-EDDA/HYNIC-TOC became commercially available in 2003, gradually substituting the 111-indium labeled analog – Octreoscan. The majority of clinical research on 99mTc-EDDA/HYNIC-TOC was focused on the neuroendocrine tumors. Gabriel et al. reported high sensitivity (88%) and specificity (94%) of this method in a group of 88 patients with neuroendocrine tumors except insulinoma [29]. High diagnostic utility in this clinical setting was confirmed by Chrapko et al. [30]. Similarly high diagnostic accuracy of another analog, 99mTc-EDDA/HYNIC-TATE was found by authors from Cracow [35]. Some diagnostic utility of 99mTc-EDDA/HYNIC-TOC scintigraphy was also reported in patients with solitary pulmonary nodule [36].

In our center, more than 1000 SRS using 99mTc-EDDA/HYNIC-TOC were performed in recent 12 years. Majority of patients were referred for the diagnosis of neuroendocrine tumors. The second group of indications were thyroid tumors. SRS was performed only in highly selected patients with medullary thyroid carcinoma and in DTC in whom standard imaging methods failed to detect foci of the disease. Previously, we documented a relatively high diagnostic utility of 99mTc-EDDA/HYNIC-TOC in patients with asymptomatic hypercalcitoninemia in course of medullary thyroid carcinoma. The overall sensitivity was 79.5%, specificity 83.3%, positive predictive value 96.9% and negative predictive value 38.5% [31]. In current study, our experiences with this method in patients with DTC recurrence manifested by asymptomatic hyperthyroglobulinemia are summarized. In this group of patients the results were quite similar: sensitivity – 69.0%, specificity – 78.5%, positive predictive value – 90.6%, negative predictive value – 45.8%.

In a similar study performed in Innsbruck, sensitivity of SRS using 99mTc-EDDA/HYNIC-TOC was similar to that obtained in our study (66%). Comparison with PET with 18F-FDG in the same patient cohort showed its better performance in terms of lesion detection (sensitivity 87%) [16]. In our patient group not all patients were referred for a PET-CT study, so a head-to-head comparison was not possible.

Diagnostic performance of 99mTc-EDDA/HYNIC-TOC may be also compared to 111-Indium-labeled compound. In earlier years several studies were published with inconsistent results. Sensitivity of 111In-octreotide (Octrescan) in patients with DTC ranged from 20% to 100% [20-23, 37-39]. Such a wide range of results was caused by different classification criteria, wide range of tumor stage, different levels of Tg and in some cases poor statistical quality due to low number of subjects. One of the most similar patient cohort was studies by Glammarile et al. [21]. Among 43 patients with elevated Tg and similar distribution of histopathological diagnosis to our study (20 papillary thyroid carcinoma, 9 – follicular, 8 – oxyphilic) 22 patients showed positive SRS (51%), i.e. less than in our study. Although comparison of two methods in two patient cohorts should not result in clear conclusions, in this case the favorable results obtained with 99mTc-EDDA/HYNIC-TOC can be easily supported. The main cause of this difference is physical characteristics of gamma radiation emitted by two radionuclides: 99mTc and 111In. Apart from the image quality (spatial resolution) that is adversely affected by higher energy of 111In, this radionuclide may be safely used in lower doses than 99mTc due to much longer physical half-life of 67 h versus 6 h and higher dose equivalent [40].

Efficacy of SRS using 99mTc-EDDA/HYNIC-TOC was not influenced by patients’ age, time since diagnosis and cumulative radioiodine activity. There was however clear correlation with the stimulated Tg concentration. Patients with positive SRS had higher Tg values than those with negative SRS. The scan was rarely positive in patients with Tg below 10 ng/ml (11%). This finding can be compared with published results of PET using 18F-FDG. In a study performed on a PET scanner without CT also 11-13% patients with Tg of 10 ng/ml had positive 18F-FDG study [7]. However, in a study performed with the use of a hybrid PET/CT scanner this percentage was much higher – 43-53% [41, 42].

In the presented study, clinical utility of 99mTc-EDDA/HYNIC-TOC was demonstrated. It must be stressed that these results were obtained on a highly selected group of patients showing signs of dedifferentiation. Treatment options in this patient subgroup is limited. Radioiodine treatment is not effective any more leading to unnecessary radiation burden. Attempts to use chemotherapy did not show sufficient efficacy [43]. Radiation therapy is used sometimes but it is restricted only to localized process. In general, prognosis in patients with dedifferentiation is much worse than in uncomplicated DTC. 5-year survival in patients with pulmonary metastases is ca. 60% if lesions are iodine-avid and only 30% in the absence of iodine uptake [44-46]. Among possible treatment options peptide receptor radionuclide therapy (PRRT) with somatostatin analogs labeled with beta-emitters could be an interesting option. The analogues labeled with beta-emitters (yttrium-90 or lutetium-177) were found to provide encouraging results in patients with disseminated forms of neuroendocrine tumors (NET) [47, 48]. Demonstration of somatostatin receptor expression by the means of SRS is a crucial criterion to qualify to such an experimental treatment. The results of PRRT in DTC in our center have been published elsewhere [49]. PRRT was generally well-tolerated but the outcome was rather poor in majority of cases of radioiodine-refractory DTC.

In summary, SRS using 99mTc-EDDA/HYNIC-TOC is useful in the detection of disease foci in patients with radioiodine-refractory DTC. The method shows acceptable sensitivity and specificity that is however not sufficient to recommend it as a routine imaging modality. Positive SRS is more likely to occur in patients with highly elevated thyroglobulin concentrations. SRS plays complementary role to other imaging techniques including PET/CT with 18F-FDG.

References

  1. Schlumberger M, Pacini F. Thyroid tumors. Editions Nucleon. Paris 2003.
  2. Verkooijen RB, Rietbergen D, Smit JW, Romijn JA, Stokkel MR A new functional parameter measured at the time of ablation that can be used to predict differentiated thyroid cancer recurrence during follow-up. Eur J Endocrinol 2007; 156: 41-47.
  3. Jukkola A, Bloigu R, Ebeling T Salmela P, Blanco G. Prognostic factors in differentiated thyroid carcinomas and their implications for current staging classifications. Endocr Relat Cancer 2004; 11: 571-579.
  4. Jarząb B, Dedecjus M, Handkiewicz-Junak D et al. Diagnostics and Treatment of Thyroid Carcinoma. Endokrynol Pol 2016; 67: 74-107.
  5. Lazar V Bidart JM, Caillou B et al. Expression of the Na+/I-symporter gene in human thyroid tumors: a comparison study with other thyroid-specific genes. J Clin Endocrinol Metab 1999; 84: 3228-3234.
  6. Perez CA, Santos ES, Arango BA, Raez LE, Cohen EE. Novel molecular targeted therapies for refractory thyroid cancer. Head Neck 2012; 34: 736-745.
  7. Durante C, Puxeddu E, Ferretti E et al. BRAF mutations in papillary thyroid carcinomas inhibit genes involved in iodine metabolism. J Clin Endocrinol Metab 2007; 92: 2840-2843.
  8. Hodak SP Carty SE. Radioiodine-resistant differentiated thyroid cancer: hope for the future. Oncology (Williston Park, N.Y) 2009; 23: 775-776.
  9. Treglia G, Bertagna F, Piccardo A, Giovanella L. 131I whole-body scan or 18FDG PET/CT for patients with elevated thyroglobulin and negative ultrasound? Clin Translat imaging 2013; 1: 175-183.
  10. Bertagna F, Biasiotto G, Orlando E, Bosio G, Giubbini R. Role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography in patients affected by differentiated thyroid carcinoma, high thyroglobulin level, and negative 131I scan: review of the literature. Jpn J Radiol 2010; 28: 629-636.
  11. Treglia G, Annunzita S, Muoio B, Salvatori M, Ceriani L, Giovanella L. The role of fluorine-18-fluorodeoxyglucose positron emission tomography in aggressive histological subtypes of thyroid cancer: an overview. Int J Endocrinol 2013; 2013: 856189.
  12. Riemann B, Uhrhan K, Dietlein M et al. Diagnostic value and therapeutic impact of 18F-FDGPET/CT in differentiated thyroid cancer: results of a German multicentre study. Nuklearmedizin 2013; 52: 1-6.
  13. Marcus C, Whitworth PW, Surasi DS, Pai SI, Subramaniam RM. PET/CT in the management of thyroid cancers. AJR Am J Roentgenol 2014; 202: 1316-1329.
  14. Robbins RJ, Wan Q, Grewal RK et al. Real-time prognosis for metastatic thyroid carcinoma based on 2-[18F]fluoro-2-deoxy-D-glucose-positron emission tomography scanning. J Clin Endocrinol Metab 2006; 91: 498-505.
  15. Treglia G, Muoio B, Giovanella L, Salvatori M. The role of positron emission tomography and positron emission tomography/computed tomography in thyroid tumours: an overview. Eur Arch Otorhinolaryngol 2013; 270: 1783-1787.
  16. Gabriel M, Froehlich F, Decristoforo C et al. 99m-Tc-EDDA/HYNIC-TOC and 18F-FDG in thyroid cancer patients with negative 131I whole-body scans. Eur J Nucl Med Mol imaging 2004; 31: 330-341.
  17. Nahas Z, Goldenberg D, Fakhry C et al. The role of positron emission tomography/computed tomography in the management of recurrent papillary thyroid carcinoma. Laryngoscope 2005; 115: 237-243.
  18. Tenenbaum F, Lumbroso J, Schlumberger M, Caillou B, Fragu P, Parmentier C. Radiolabeled somatostatin analog scintigraphy in differentiated thyroid carcinoma. J Nucl Med 1995; 36: 807-810.
  19. Stokkel MP Reigman HI, Verkooijen RB, Smit JW. Indium-111-Octreotide scintigraphy in differentiated thyroid carcinoma metastases that do not respond to treatment with high-dose I-131. J Cancer Res Clin Oncol 2003; 129: 287-294.
  20. Baudin E, Schlumberger M, Lumbroso J, Travagli JP, Caillou B, Permentier C, Octreotide scintigraphy in patients with differentiated thyroid carcinoma: contribution for patints with negative radioiodine scan. J Clin Endocrinol Metab 1996; 81: 2541-2544.
  21. Giammarile F, Houzard C, Bournaud C, Hafdi Z, Sassolas G, Borson-Chazot F Diagnostic management of suspected metastatic thyroid carcinoma: clinical value of octreotide scintigraphy in patient with negative high-dose radioiodine scans. Eur J Endocrinol 2004; 150: 277-283.
  22. Postema PT, De Herder WW, Reubi JC et al. Somatostatin receptor scintigraphy in non-medullary thyroid cancer. Digestion 1996; 57: 36-37.
  23. Garin E, Devillers A, Le Cloirec J et al. Use of indium-111 pentetreotide somatostatin receptor scintigraphy to detect reccurent thyroid carcinoma in patients without detecteble iodine uptake. Eur J Nucl Med 1998; 25: 687-694.
  24. Valli N, Catargi B, Ronci N et al. Evaluation of indium-111 pentetreotide somatostatin receptor scintigraphy to detect recurrent thyroid carcinoma in patients with negative radioiodine scintigraphy. Thyroid 1999; 9: 583-589.
  25. Bangard M, Behe M, Guhlke S et al. Detection of somatostatin receptor-positive tumours using the new 99mTc-tricine-HYNIC-d-Phe1-Tyr3-octreotide: first results in patients and comparison with 111In-DTPA-d-Phe1-octreotide. Eur J Nucl Med Mol Imag 2000; 27: 628-637.
  26. Decristoforo C, Melendez-Alafort L, Sosabowski JK, Mather SJ. 99m-Tc-HYNIC-[Tyr3]-octreotide for imaging somatostatin-positive tumors: preclinical evaluation and comparison with 111In-octreotide. J Nucl Med 2000; 41: 1114-1119.
  27. Decristoforo C, Mather SJ, Cholewinski W, Donnemiller E, Riccabona G, Moncayo R. 99m-TcEDDA/HYNIC-TOC: a new 99m-Tc-labelled radiopharmaceutical for imaging somatostatin receptor-positive tumors: first clinical result and intra-patient comparision with 111-In-labelled octreotide derivates. Eur J Nucl Med 2000; 27: 1318-1325.
  28. Gabriel M, Decristoforo C, Donnemiller E et al. An intrapatient comparison of 99m-Tc EDDA/HYNIC-TOC with 111-In-DTPA-octreotide for diagnosis of somatostatin receptor expressing tumors. J Nucl Med 2003; 44: 708-716.
  29. Gabriel M, Muehllechner P, Decristoforo C et al. 99mTc-EDDA/HYNIC-Tyr(3)-octreotide for staging and follow-up of patients with neuroendocrine gastro-entero-pancreatic tumors. Q J Nucl Med Mol imaging 2005; 49: 237-244.
  30. Chrapko BE, Nocuń A, Gołębiewska R et al. 99mTc-EDDA/HYNIC-TOC somatostatin receptor scintigraphy in daily clinical practice. Med Sci Monit 2010; 16: 35-44.
  31. Czepczyński R, Parisella MG, Kosowicz J et al. Somatostatin receptor scintigraphy using 99mTc-EDDA/HYNIC-TOC in patients with medullary thyroid carcinoma. Eur J Nucl Med Mol imaging 2007; 34: 1635-1645.
  32. Jarząb B, Sporny S, Lange D, Włoch J, Lewiński A. Diagnosis and treatment of thyroid carcinoma–Polish guidelines. Endokrynol Pol 2010; 61: 518-568.
  33. Luster M, Clarke SE, Dietlein M et al. Guidelines for radiotherapy of differentiated thyroid kancer. Eur J Nucl Med Mol imaging 2008; 35: 1941-5199.
  34. Reubi JC, Kvols L, Krenning E, Lamberts SWJ. Distribution of somatostatin receptors in normal and tumor tissue. Metabolism 1990; 39 (suppl 2): 78-81.
  35. Hubalewska-Dydejczyk A, Fross-Baron K, Mikołajczak R et al. 99mTc-EDDA/HYNIC-octreotate scintigraphy, an efficient method for the detection and staging of carcinoid tumours: results of 3 years’ experience. Eur J Nucl Med Mol imaging 2006; 33: 1123-1133.
  36. Płachcińska A, Mikołajczak R, Maecke H et al. Clinical usefulness of 99mTc-EDDA/HYNIC-TOC scintigraphy in oncological diagnostics: a pilot study. Cancer Biother Radiopharm 2004; 19: 261-270.
  37. Haslinghuis LM, Krenning EP De Herder WW, Reijs AE, Kwekkeboom DJ. Somatostatin receptor scintigraphy in the follow-up of patients with differentiated thyroid cancer. J Endocrinol Invest 2001; 24: 415-422.
  38. Christian JA, Cook GJ, Harmer C. Indium-111-labelled octreotide scintigraphy in the diagnosis and management of non-iodine avid metastatic carcinoma of the thyroid. Br J Cancer 2003; 89: 258-261.
  39. Stokkel MP Reigman HI, Verkooijen RB, Smit JW. Indium-111-Octreotide scintigraphy in differentiated thyroid carcinoma metastases that do not respond to treatment with high-dose I-131. J Cancer Res Clin Oncol. 2003; 129: 287-294.
  40. Decristoforo C, Mather SJ. Technetium-99m somatostatin analogues: effect of labelling methods and peptide sequence. Eur J Nucl Med 1999; 26: 869-876.
  41. Stangierski A, Kaznowski J, Woliński K et al. The usefulness of fluorine-18 fluorodeoxyglucose PET in the detection of recurrence in patients with differentiated thyroid cancer with elevated thyroglobulin and negative radioiodine whole-body scan. Nucl Med Cummun 2016; 37: 935-938.
  42. Trybek T, Kowalska A, Lesiak J, Młynarczyk J. The role of 18F-Fluorodeoxyglucose Positron Emission Tomography in patients with suspected recurrence or metastatic differentiated thyroid carcinoma with elevated serum thyroglobulin and negative I-131 whole body scan. Nucl Med Rev Cent East Eur 2014; 17: 87-93.
  43. Haugen BR, Alexander EK, Bible KC et al. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid 2016; 26: 1-133.
  44. Sherman SI. Thyroid carcinoma. Lancet 2003; 361: 501-511.
  45. Maxon HR, Smith HS. Radioiodine-131 in the diagnosis and treatment of metastatic well differentiated thyroid cancer. Endocrinol Metab Clin North Am 1990; 19: 685-718.
  46. Sisson JC, Giordano TJ, Jamadar DA. 131-I treatment of micronodular pulmonary metastases from papillary thyroid carcinoma. Cancer 1996; 78: 2184-2192.
  47. Bodei L, Cremonesi M, Grana C et al. Receptor radionuclide therapy with 90Y-[DOTA]0-Tyr3-octreotide (90Y-DOTATOC) in neuroendocrine tumours. Eur J Nucl Med Mol imaging 2004; 31: 1038-1046.
  48. Kunikowska J, Królicki L, Hubalewska-Dydejczyk A, Mikołajczak R, Sowa-Staszczak A, Pawlak D. Clinical results of radionuclide therapy of neuroendocrine tumours with 90Y-DOTATATE and tandem 90Y/177Lu-DOTATATE: which is a better therapy option? Eur J Nucl Med Mol Imaging 2011; 38: 1788-1797.
  49. Czepczyński R, Matysiak-Grześ M, Gryczyńska M et al. Peptide receptor radionuclide therapy of differentiated thyroid cancer: efficacy and toxicity. Arch Immunol Ther Exp (Warsz) 2015; 63: 147-154.

Correspondence to:
Dr Rafał Czepczyński, MD, PhD
Department of Endocrinology and Metabolism,
Poznan University of Medical Sciences, Poznan, Poland
E-mail: rafal.czepczynski@gmail.com

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