Orthotopic Thyroid Research Articles

A rare case of double ectopic thyroid without orthotopic thyroid gland

Abstract We report an extremely rare case of concurrent lingual thyroid and thyroglossal duct thyroid without orthotopic thyroid gland in a paediatric patient with hypothyroidism. The clinical record highlights the importance of ultrasonography and thyroxine therapy in the management of this rare clinical entity.

Development and characterization of six new human papillary thyroid carcinoma cell lines.

Cell lines are a widely used tool in cancer research. However, despite the relatively high incidence of papillary thyroid carcinoma (PTC), there are only four PTC cell lines available for international research audience. The objective of this study was to establish and characterize new PTC cell lines that represent primary tumor biology. Surgical specimens were obtained to generate PTC cell lines. Short tandem repeat profiling was used to confirm the uniqueness of the cell lines against databases of known cell lines and mutations were assessed using Sequenom. The expression of thyroid-specific genes was examined using real-time PCR. Tumorigenicity was determined using an orthotopic thyroid xenograft tumor mouse model. Six PTC cell lines (five conventional PTCs and one follicular variant of PTC) were generated and found to be unique when compared by short tandem repeat profiling against databases of all existing cell lines. The five conventional PTC cell lines carry the BRAF V600E mutation and the follicular variant of PTC cell line had an NRAS mutation. Five of the six cell lines had a mutation in the promoter of the human telomerase reverse transcriptase gene. None of the cell lines have RET/PTC rearrangements. Three cell lines were tumorigenic in the orthotopic thyroid xenograft tumor mouse model. These five characterized conventional PTC cell lines and the unique follicular variant of PTC cell line should be valuable reagents for thyroid cancer research. The three tumorigenic cell lines can be used for in vivo testing of targeted therapeutic and novel agents.

Double Tongues

A 1-year-old Chinese boy presented with a mass at the base of his tongue with dysphagia. The distal end of the lesion could be put out of his mouth, making a "double tongue" appearance. Before surgery, serum test showed euthyroidism. Thyroid scintigraphy showed good function of the orthotopic thyroid, yet no uptake by the lesion, excluding ectopic thyroid. En bloc resection was performed. Histopathology demonstrated aberrant salivary tissues. Our case indicates that differential diagnosis between ectopic salivary tissues and ectopic thyroid should be borne in mind when treating patients with double tongues.

Blocks to thyroid cancer cell apoptosis can be overcome by inhibition of the MAPK and PI3K/AKT pathways

Current treatment for recurrent and aggressive/anaplastic thyroid cancers is ineffective. Novel targeted therapies aimed at the inhibition of the mutated oncoprotein BRAFV600E have shown promise in vivo and in vitro but do not result in cellular apoptosis. TNF-related apoptosis-inducing ligand (TRAIL) induces apoptosis in a tumor-selective manner by activating the extrinsic apoptotic pathway. Here, we show that a TRAIL-R2 agonist antibody, lexatumumab, induces apoptosis effectively in some thyroid cancer cell lines (HTh-7, TPC-1 and BCPAP), while more aggressive anaplastic cell lines (8505c and SW1736) show resistance. Treatment of the most resistant cell line, 8505c, using lexatumumab in combination with the BRAFV600E inhibitor, PLX4720, and the PI3K inhibitor, LY294002, (triple-drug combination) sensitizes the cells by triggering both the extrinsic and intrinsic apoptotic pathways in vitro as well as 8505c orthotopic thyroid tumors in vivo. A decrease in anti-apoptotic proteins, pAkt, Bcl-xL, Mcl-1 and c-FLIP, coupled with an increase in the activator proteins, Bax and Bim, results in an increase in the Bax to Bcl-xL ratio that appears to be critical for sensitization and subsequent apoptosis of these resistant cells. Our results suggest that targeting the death receptor pathway in thyroid cancer can be a promising strategy for inducing apoptosis in thyroid cancer cells, although combination with other kinase inhibitors may be needed in some of the more aggressive tumors initially resistant to apoptosis.

The Next Generation of Orthotopic Thyroid Cancer Models: Immunocompetent Orthotopic Mouse Models of BRAFV600E-Positive Papillary and Anaplastic Thyroid Carcinoma

While the development of new treatments for aggressive thyroid cancer has advanced in the last 10 years, progress has trailed headways made with other malignancies. A lack of reliable authenticated human cell lines and reproducible animal models is one major roadblock to preclinical testing of novel therapeutics. Existing xenograft and orthotopic mouse models of aggressive thyroid cancer rely on the implantation of highly passaged human thyroid carcinoma lines in immunodeficient mice. Genetically engineered models of papillary and undifferentiated (anaplastic) thyroid carcinoma (PTC and ATC) are immunocompetent; however, slow and stochastic tumor development hinders high-throughput testing. Novel models of PTC and ATC in which tumors arise rapidly and synchronously in immunocompetent mice would facilitate the investigation of novel therapeutics and approaches. We characterized and utilized mouse cell lines derived from PTC and ATC tumors arising in genetically engineered mice with thyroid-specific expression of endogenous Braf(V600E/WT) and deletion of either Trp53 (p53) or Pten. These murine thyroid cancer cells were transduced with luciferase- and GFP-expressing lentivirus and implanted into the thyroid glands of immunocompetent syngeneic B6129SF1/J mice in which the growth characteristics were assessed. Large locally aggressive thyroid tumors form within one week of implantation. Tumors recapitulate their histologic subtype, including well-differentiated PTC and ATC, and exhibit CD3+, CD8+, B220+, and CD163+ immune cell infiltration. Tumor progression can be followed in vivo using luciferase and ex vivo using GFP. Metastatic spread is not detected at early time points. We describe the development of the next generation of murine orthotopic thyroid cancer models. The implantation of genetically defined murine BRAF-mutated PTC and ATC cell lines into syngeneic mice results in rapid and synchronous tumor formation. This model allows for preclinical investigation of novel therapeutics and/or therapeutic combinations in the context of a functional immune system.

Thioredoxin interacting protein (TXNIP) is a novel tumor suppressor in thyroid cancer

BackgroundThyroid cancer is the most common endocrine malignancy, and many patients with metastatic differentiated thyroid cancer (DTC), poorly differentiated thyroid cancer (PDTC), and anaplastic thyroid cancer (ATC) fail to respond to conventional therapies, resulting in morbidity and mortality. Additional therapeutic targets and treatment options are needed for these patients. We recently reported that peroxisome proliferator-activated receptor gamma (PPARγ) is highly expressed in ATC and confers an aggressive phenotype when overexpressed in DTC cells.MethodsMicroarray analysis was used to identify downstream targets of PPARγ in ATC cells. Western blot analysis and immunohistochemistry (IHC) were used to assess thioredoxin interacting protein (TXNIP) expression in thyroid cancer cell lines and primary tumor specimens. Retroviral transduction was used to generate ATC cell lines that overexpress TXNIP, and assays that assess glucose uptake, viable cell proliferation, and invasion were used to characterize the in vitro properties of these cells. An orthotopic thyroid cancer mouse model was used to assess the effect of TXNIP overexpression in ATC cell lines in vivo.ResultsUsing microarray analysis, we show that TXNIP is highly upregulated when PPARγ is depleted from ATC cells. Using Western blot analysis and IHC, we show that DTC and ATC cells exhibit differential TXNIP expression patterns. DTC cell lines and patient tumors have high TXNIP expression in contrast to low or absent expression in ATC cell lines and tumors. Overexpression of TXNIP decreases the growth of HTh74 cells compared to vector controls and inhibits glucose uptake in the ATC cell lines HTh74 and T238. Importantly, TXNIP overexpression in T238 cells results in attenuated tumor growth and decreased metastasis in an orthotopic thyroid cancer mouse model.ConclusionsOur findings indicate that TXNIP functions as a tumor suppressor in thyroid cells, and its downregulation is likely important in the transition from differentiated to advanced thyroid cancer. These studies underscore the potential of TXNIP as a novel therapeutic target and prognostic indicator in advanced thyroid cancer.

Ectopic Thyroid Gland: Description of a Case and Review of the Literature

The clinical occurrence of ectopic thyroid gland is an infrequently encountered condition, resulting from a developmental abnormality during the migration of the thyroid anlage from the floor of the primitive foregut to its final position in the neck. It can be found along the way of thyroid descent, in the midline, or laterally in the neck or even in the mediastinum or under the diaphragm. This condition is often asymptomatic, whereas symptoms could be related to ectopic thyroid size, to its relationships with surrounding organs or to diseases affecting the ectopic thyroid in the same way they involve orthotopic glands. Sometimes, a growing mass can lead to the clinical suspicion of a tumor disease. On the other hand, thyroid ectopy must be distinguished from metastasis of thyroid cancer. Scintigraphy and ultrasonography are the main diagnostic means for evaluating ectopic thyroid tissue, whereas fine needle aspiration could be useful in the presence of a nodular ectopic gland or when the coexistence of an orthotopic thyroid can arise the suspicion of a metastasis from a thyroid cancer. Surgical removal is indicated in symptomatic cases, whereas radioiodine ablation is reserved to recurrent disease. In this paper we report an emblematic case of ectopic thyroid gland and a review of the literature dealing with this condition.

Unexpected Diagnosis of Thyroid Storm in a Young Child Referred for Urgent Lung Perfusion Imaging

A 2-year-old girl with cardiorespiratory distress and suspected pulmonary embolism (PE) was referred for urgent lung perfusion scintigraphy, proven negative for perfusion defects but unexpectedly revealing an enlarged orthotopic thyroid. This finding was, under the circumstances, considered as suggestive of thyroid storm (TS), subsequently confirmed by thyroid hormones measurement. A (99m)TcO(4)(-) thyroid scan 1 week later showed a homogenously enlarged thyroid with high tracer uptake. Both PE and TS are rare but serious pediatric conditions with partially overlapping presentations. In the present case, the unbounded (99m)Tc fraction avidly taken by the overfunctioning thyroid suggested the correct, clinically unsuspected, diagnosis.

Ectopic Thyroid Tissue in the Adrenal Gland: A Report of Two Cases with Pathogenetic Implications

Ectopic thyroid tissue is usually found anywhere along the embryonic descent pathway of the medial thyroid anlage from the tongue to the trachea (Wölfler area). However, ectopic thyroid tissue in the adrenal gland (ETTAG) is not easy to understand on the basis of thyroid embryology; because it is so rare, the possibility of metastasis should first be considered. Here, we describe two cases of ETTAG with pathogenetic implications and review the associated literature. Two cases of ETTAG presented as incidental cystic adrenal masses in adult females, one having a congenital hernia of Morgagni. The ETTAG was histologically indistinguishable from normal orthotopic thyroid tissue, and its follicular nature was confirmed by immunohistochemical positivity for thyroglobulin, thyroperoxidase, thyroid transcription factor-1 (TTF-1/Titf-1/Nkx2.1), cytokeratin AE1/AE3, cytokeratin 7, pendrin, human sodium iodide symporter, paired box gene 8, and forkhead box E1 (TTF-2), as well as positivity for the messenger RNA of the thyroglobulin gene by in situ hybridization analysis. No C cells (negativity for calcitonin, chromogranin, and synaptophysin) were present. Neither BRAF nor KRAS mutations were detected with real-time polymerase chain reaction analysis. Further work-up did not show evidence of thyroid malignancy. ETTAG is a rare finding, with only seven cases reported; women are much more frequently affected than men (8:1), and it usually presents in the fifth decade (mean age 54, range 38-67) as a cystic adrenal mass incidentally discovered on abdominal ultrasonography and/or in computed tomography images. ETTAG is composed of normal follicular cells without C cells. The expression of some transcription factors (TTF-1, paired box gene 8, and FOXE1) involved in development and/or migration of the medial thyroid anlage is preserved. Coexistence of a congenital hernia of Morgagni in one patient suggests an overdescent of medial thyroid anlage-derived cells in its pathogenesis. Although ETTAG pathogenesis remains unknown, the lack of C cells together with the coexistence of a congenital defect of the anterior diaphragm (hernia of Morgagni) in one of our patients could suggest an overdescent of medial thyroid anlage-derived cells in the origin of this heterotopia.

Sorafenib and Thyroid Cancer

Sorafenib (Nexavar) is a multikinase inhibitor, which has demonstrated both anti-proliferative and anti-angiogenic properties in vitro and in vivo, inhibiting the activity of targets present in the tumor cell [c-RAF (proto-oncogene serine/threonine-protein kinase), BRAF, (V600E)BRAF, c-KIT, and FMS-like tyrosine kinase 3] and in tumor vessels (c-RAF, vascular endothelial growth factor receptor-2, vascular endothelial growth factor receptor-3, and platelet-derived growth factor receptor β). For several years, sorafenib has been approved for the treatment of hepatocellular carcinoma and advanced renal cell carcinoma. After previous studies showing that sorafenib was able to inhibit oncogenic RET mutants, (V600E)BRAF, and angiogenesis and growth of orthotopic anaplastic thyroid cancer xenografts in nude mice, some clinical trials demonstrated the effectiveness of sorafenib in advanced thyroid cancer. Currently, the evaluation of the clinical safety and efficacy of sorafenib for the treatment of advanced thyroid cancer is ongoing. This article reviews the anti-neoplastic effect of sorafenib in thyroid cancer. Several completed (or ongoing) studies have evaluated the long-term efficacy and tolerability of sorafenib in patients with papillary and medullary aggressive thyroid cancer. The results suggest that sorafenib is a promising therapeutic option in patients with advanced thyroid cancer that is not responsive to traditional therapeutic strategies.

Functioning thyroglossal cyst and concurrent ectopic thyroid in the floor of the mouth without an orthotopic thyroid gland

We report the case of a 20-year-old man with a constellation of anomalies - a functional thyroglossal cyst and concurrent ectopic thyroid in the floor of the mouth, without an orthotopic thyroid gland. To our knowledge, this is the third such report in the otolaryngology literature. It is important to be aware of the possibility of concurrent ectopic thyroid and thyroglossal cyst in the absence of an orthotopic thyroid gland. The majority of reported cases of thyroid ectopy occur at the base of the tongue. The occurrence of an ectopic thyroid in the floor of the mouth is both unusual and not amenable to clinical examination. Even if there is good uptake on nuclear imaging, the ectopic thyroid may be hypofunctioning. We discuss the importance of thyroid imaging, as well as the need for preoperative imaging and an appropriate management strategy in the treatment of patients with this triad of anomalies.

An Orthotopic Mouse Model of Anaplastic Thyroid Carcinoma

Several types of animal models of human thyroid carcinomas have been established, including subcutaneous xenograft and orthotopic implantation of cancer cells into immunodeficient mice. Subcutaneous xenograft models have been valuable for preclinical screening and evaluation of new therapeutic treatments. There are a number of advantages to using a subcutaneous model; 1) rapid, 2) reproducible, and 3) tumor establishment, growth, and response to therapeutic agents may be monitored by visual inspection. However, substantial evidence has shed light on the short-comings of subcutaneous xenograft models1-3. For instance, medicinal treatments demonstrating curative properties in subcutaneous xenograft models often have no notable impact on the human disease. The microenvironment of the site of xenographic transplantation or injection lies at the heart of this dissimilarity.Orthotopic tumor xenograft models provide a more biologically relevant context in which to study the disease. The advantages of implanting diseased cells or tissue into their anatomical origin equivalent within a host animal includes a suitable site for tumor-host interactions, development of disease-related metastases and the ability to examine site-specific influence on investigational therapeutic remedies. Therefore, orthotopic xenograft models harbor far more clinical value because they closely reproduce human disease. For these reasons, a number of groups have taken advantage of an orthotopic thyroid cancer model as a research tool4-7.Here, we describe an approach that establishes an orthotopic model for the study of anaplastic thyroid carcinoma (ATC), which is highly invasive, resists treatment, and is virtually fatal in all diagnosed patients. Cultured ATC cells are prepared as a dissociated cellular suspension in a solution containing a basement membrane matrix. A small volume is slowly injected into the right thyroid gland. Overall appearance and health of the mice are monitored to ensure minimal post-operative complications and to gauge pathological penetrance of the cancer. Mice are sacrificed at 4 weeks, and tissue is collected for histological analysis. Animals may be taken at later time-points to examine more advance progression of the disease. Production of this orthotopic mouse model establishes a platform that accomplishes two objectives: 1) further our understanding of ATC pathology, and 2) screen current and future therapeutic agents for efficacy in combating ATC.

An Orthotopic Mouse Model of Anaplastic Thyroid Carcinoma

Several types of animal models of human thyroid carcinomas have been established, including subcutaneous xenograft and orthotopic implantation of cancer cells into immunodeficient mice. Subcutaneous xenograft models have been valuable for preclinical screening and evaluation of new therapeutic treatments. There are a number of advantages to using a subcutaneous model; 1) rapid, 2) reproducible, and 3) tumor establishment, growth, and response to therapeutic agents may be monitored by visual inspection. However, substantial evidence has shed light on the short-comings of subcutaneous xenograft models1-3. For instance, medicinal treatments demonstrating curative properties in subcutaneous xenograft models often have no notable impact on the human disease. The microenvironment of the site of xenographic transplantation or injection lies at the heart of this dissimilarity. Orthotopic tumor xenograft models provide a more biologically relevant context in which to study the disease. The advantages of implanting diseased cells or tissue into their anatomical origin equivalent within a host animal includes a suitable site for tumor-host interactions, development of disease-related metastases and the ability to examine site-specific influence on investigational therapeutic remedies. Therefore, orthotopic xenograft models harbor far more clinical value because they closely reproduce human disease. For these reasons, a number of groups have taken advantage of an orthotopic thyroid cancer model as a research tool4-7. Here, we describe an approach that establishes an orthotopic model for the study of anaplastic thyroid carcinoma (ATC), which is highly invasive, resists treatment, and is virtually fatal in all diagnosed patients. Cultured ATC cells are prepared as a dissociated cellular suspension in a solution containing a basement membrane matrix. A small volume is slowly injected into the right thyroid gland. Overall appearance and health of the mice are monitored to ensure minimal post-operative complications and to gauge pathological penetrance of the cancer. Mice are sacrificed at 4 weeks, and tissue is collected for histological analysis. Animals may be taken at later time-points to examine more advance progression of the disease. Production of this orthotopic mouse model establishes a platform that accomplishes two objectives: 1) further our understanding of ATC pathology, and 2) screen current and future therapeutic agents for efficacy in combating ATC.

Never too late to discover some extra thyroid tissue

thyroid embryogenesis, in it’s normal migration process from the floor of the primitive foregut to the pretracheal location. It’s prevalence is 1 per 100000 - 300000 in general population and 1 per 4000-8000 in patients with thyroid disease. This condition is more common in females, Asians and may occur at any age, although it’s most common at younger ages. The mean age of presentation is 40,5 years. The exact mechanisms responsible are still unclear but many transcription factors appear to play a key role such as TITF1/NKX2-1, PAX 8, HHEX and FOXE 1. Thyroid ectopy may also have familial/hereditary background: heterozygous mutations in PAX 8 and expression of the Thyroid-Per-Oxidase and Thyroglobulin Genes. The most frequent (about 90%) location of ectopic thyroid tissue is at the base of the tongue and in those, 70 – 75% of cases it’s the only thyroid tissue present. The most common symptoms are related to the growth of lingual thyroid (dysphagia, dysphonia, sleep apnea or even respiratory obstruction and hemorrhage) and hypothyroidism, specially in the absence of orthotopic thyroid.

A Case of Contemporaneous Occurrence of Thyroglossal Duct Cyst and Lingual Thyroid without the Orthotopic Thyroid Gland

Thyroglossal duct cyst (TGDC) and lingual thyroid (LT) are relatively common developmental anomalies of the thyroid gland. The former is the most common congenital malformation in childhood, usually presenting as a midline neck mass. The latter stems from the existence of thyroid tissue at the foramen cecum, presenting as a tongue base mass. Each of these can arise without the orthotopic thyroid gland, but the co-existence of all three anomalies is extremely rare. We report a 71year-old woman with all three of these anomalies. To the best of our knowledge, this is the third report of such a case in the English literature.

Dual ectopic thyroid in the presence of atrophic orthotopic thyroid gland in a patient with acquired hypothyroidism: Evaluation with hybrid Single-Photon Emission Computed Tomography/Computed Tomography

Ectopic thyroid tissue (ETT) refers to all cases in which the thyroid gland is present at a location other than its usual site. The prevalence of ETT is approximately one per 100,000 to 300,000 persons and is reported to occur in one in 4,000 to 8,000 patients with thyroid disease. Multiple ectopia of thyroid is extremely rare. Multiple ectopia in the presence of orthotopic thyroid gland is extremely rare. We report a 13-year-old boy with stunted growth and developmental delay caused due to acquired hypothyroidism. Technetium scan performed as per management protocol identified dual ectopia of thyroid. The role of hybrid Single-Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) in the localization of the sites of ETT is also highlighted.

Ectopic Thyroid Tissue in the Thyroglossal Cyst Duct: Rare Clinical Entity with Review of Literature

ABSTRACT The ectopic thyroid tissue is a rare developmental abnormality during embryogenesis where the thyroid gland passes from floor of the primitive foregut to its final pretracheal position. Its very important to verify the presence of a normally located normally functioning thyroid gland, thus excluding the possibility of an ectopic thyroid gland which resembles a TDC. A 12-year-old female presented to us with swelling in the midline of the neck region since 1 year. The mass moved with swallowing and protrusion of the tongue. On aspiration biopsy, a colloid material with cyst was confirmed. Imaging showed no orthotopic thyroid tissue on sonography and scintigraphy. No surgical intervention was done and as the patient was hypothyroid, levothyroxine replacement was given and the patient was advised for followup regularly. Hormonal estimation to rule out hypothyroid status and thyroid scintigraphy to detect the ectopic tissue and to see the presence of the normal orthotopic thyroid are essential investigations in evaluating thyroglossal cyst. Surgery is the treatment of choice in symptomatic lingual thyroids, with a role for radioiodine ablation in recurrent disease. Head and neck surgeons should evaluate ectopic thyroid as a differential diagnosis while evaluating mass in the midline as well as lateral neck. How to cite this article Naik SM, Halkud R, Madhu SD, Chavan P, Siddappa KT, Gupta S, Sunil KC, Moorthy S, Sinha P, Sarvadyna J. Ectopic Thyroid Tissue in the Thyroglossal Cyst Duct: Rare Clinical Entity with Review of Literature. World J Endoc Surg 2013;5(2):39-44.

Recurrent thyrotoxicosis due to hyperfunction of multiple ectopic thyroid tissue and residual thyroid lobes 15 years after thyroidectomy: Evaluation using technetium scanning and hybrid single-photon emission computed tomography/CT

Ectopic thyroid tissue (ETT) refers to all cases in which the thyroid gland is present at a location other than its usual site. Hyperthyroidism in ETT is very rare with only a few cases reported in literature. We report a 48-year-old female, a case of relapse of hyperthyroidism 15 years after thyroidectomy. Technetium scanning with hybrid single-photon emission computed tomography (SPECT)/CT showed increased trapping function in residual orthotopic thyroid lobes. Increased trapping function was also noted in two other ectopic sites. The patient was treated with radioiodine.

Hybrid SPECT/CT Evaluation of Dual Ectopia of Thyroid in the Absence of Orthotopic Thyroid Gland

Ectopic thyroid tissue (ETT) refers to all cases in which the thyroid gland is present at a location other than its usual site. The prevalence of ETT is approximately 1 per 100,000 to 300,000 persons and is reported to occur in 1 of 4000 to 8000 patients with thyroid disease. Multiple ectopia of the thyroid is extremely rare, with fewer than 35 cases published in literature to date. We report a 4-year-old girl with euthyroid and dual ectopia of thyroid without orthotopic thyroid gland. The role of hybrid SPECT/CT in the localization of the sites of ETT is also highlighted.

Assessment of Endothelin-A Receptor Expression in Subcutaneous and Orthotopic Thyroid Carcinoma Xenografts in Vivo Employing Optical Imaging Methods

Endothelin (ET) receptor dysregulation has been described in a number of pathophysiological processes, including cardiovascular disorders, renal failure, and cancer. The aim of this study was to evaluate the expression of the ET-A receptor (ET(A)R) in murine models of thyroid carcinoma using optical imaging methods. A recently developed near-infrared fluorescent tracer was first assessed in isolated artery preparations for its functional performance in comparison with known ET(A)R antagonists BQ123 and PD156707. Before evaluation of the tracer in vivo, different thyroid carcinoma cell lines were characterized with respect to their ET receptor expression by RT-PCR and autoradiography. In vivo, sc and orthotopic papillary thyroid tumor xenografts were clearly visualized by fluorescence reflectance imaging and fluorescence-mediated tomography up to 48 h after injection of the tracer. Binding specificity of the probe was demonstrated by predosing with PD156707 as a competing inhibitor. In conclusion, optical imaging with a fluorescent ET(A)R tracer allows the noninvasive imaging of tumor-associated ET(A)R expression in vivo. In the future, this technique may help surgeons to evaluate lesion dimensions in intraoperative settings (e.g. thyroidectomy).