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DOI:10.2214/AJR.07.2946
AJR 2008; 190:815-824
© American Roentgen Ray Society

Pictorial Essay

Clinical Utility of Hybrid SPECT-CT in Endocrine Neoplasia

Chirag N. Patel1, Fahmid U. Chowdhury and Andrew F. Scarsbrook

1 All authors: Department of Radiology, St. James' University Hospital, Beckett St., Leeds LS9 7TF, United Kingdom.

Received July 26, 2007; accepted after revision September 13, 2007.

 
Address correspondence to C. N. Patel (chirag.patel{at}leedsth.nhs.uk).

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Abstract
Top
 Abstract
Introduction
 Parathyroid Tumors
 Thyroid Tumors
 Neuroendocrine Tumors
 Conclusion
 References
 
OBJECTIVE. Imaging of endocrine neoplasms often involves a combination of anatomic and functional techniques including sonography, CT, MRI, and scintigraphy. Recent technologic advances have enabled hybrid imaging using SPECT-CT, which combines anatomic and functional techniques to allow accurate localization of tumors, increased detection of recurrent and metastatic disease, and exclusion of physiologic uptake.

CONCLUSION. SPECT-CT provides improved specificity and diagnostic confidence helping to guide conventional management and assess suitability for targeted radionuclide therapy.

Keywords: endocrine imaging • endocrine neoplasms • hybrid imaging • SPECT-CT


Introduction
Top
 Abstract
 Introduction
Parathyroid Tumors
 Thyroid Tumors
 Neuroendocrine Tumors
 Conclusion
 References
 
Endocrine neoplasms are a heterogeneous group of tumors and may present with a clinical syndrome as a result of hormone secretion. Functional tumors are often small and difficult to locate with conventional anatomic imaging alone. In contrast, nonfunctional tumors present later with larger or multiple lesions of uncertain clinical significance. Hybrid SPECT-CT combines accurate anatomic localization and functional characterization of endocrine neoplasms in one examination and is a major advance in the management of selected patients with endocrine malignancy. Although previous attempts to combine anatomic and functional imaging using software and visual coregistration have been time-consuming and somewhat unreliable with limited clinical use, the development of dual-technique SPECT-CT machines has resulted in a resurgence of interest in hybrid imaging. The increasing range of clinical applications of SPECT-CT has stimulated the major manufacturers to produce a range of dual-technique machines with the aim of increasing availability beyond academic institutions. Within endocrine imaging, SPECT-CT improves diagnostic accuracy by aiding localization, defining functional significance, and excluding sites of physiologic uptake [1]. This article will illustrate the role of SPECT-CT in a range of endocrine neoplasms and show the impact on diagnosis and patient management.


Parathyroid Tumors
Top
 Abstract
 Introduction
 Parathyroid Tumors
Thyroid Tumors
 Neuroendocrine Tumors
 Conclusion
 References
 
Parathyroid adenoma is the most common cause of primary hyperparathyroidism (HPT), with solitary adenomas accounting for 85% of cases. The management of patients with primary HPT has evolved from bilateral neck explorations with high success rates (90–95%) to minimally invasive surgical procedures with reduced operative morbidity and hospitalization [2]. Accurate preoperative localization is essential to guide less invasive surgery. Technetium-99m sestamibi (MIBI [methoxyisobutylisonitrile]) scintigraphy combined with high-resolution sonography has a well-established role in this setting, with a sensitivity of more than 90% [3]. The sensitivity is considerably reduced in the presence of thyroid nodules, previous neck surgery, and ectopic adenomas. SPECT-CT has an incremental value in these settings, improving localization and guiding surgical planning, especially for deep-seated adenomas (Fig. 1A, 1B), ectopic adenomas (Fig. 2A, 2B), and patients with distorted neck anatomy from previous surgery.


Figure 1
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  		Fig. 1A —57-year-old man with persistent primary hyperparathyroidism after exploratory surgery. Planar scintigram obtained 20 minutes after administration of 99mTc-MIBI [methoxyisobutylisonitrile] shows intense focal uptake in left lower neck (arrow). No corresponding abnormality was detected on high-resolution sonography.

 

Figure 2
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  		Fig. 1B —57-year-old man with persistent primary hyperparathyroidism after exploratory surgery. Fused multiplanar images from SPECT-CT acquisition localize uptake to deep-seated left inferior parathyroid adenoma lying adjacent to anterolateral border of vertebral body (arrows). This was not seen on sonography because of its position posterior to the trachea. SPECT-CT guided minimally invasive surgical intervention, which confirmed a solitary parathyroid adenoma.

 

Figure 3
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  		Fig. 2A —59-year-old man with primary hyperparathyroidism. Planar scintigrams obtained 20 minutes (top) and 2 hours (bottom) after the administration of 99mTc-MIBI [methoxyisobutylisonitrile] show focal uptake in right lower neck (arrow) and left upper thorax (arrowhead).

 

Figure 4
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  		Fig. 2B —59-year-old man with primary hyperparathyroidism. Fused multiplanar SPECT-CT images localize uptake in upper chest to small nodule just above level of aortic arch (arrowheads). There was also a right inferior parathyroid adenoma (not shown). Accurate localization greatly aided surgical planning, and ectopic parathyroid adenoma was confirmed at surgery. Ectopic adenomas account for up to 20% of parathyroid adenomas. Note physiologic tracer uptake in submandibular glands (arrows).

 

Thyroid Tumors
Top
 Abstract
 Introduction
 Parathyroid Tumors
 Thyroid Tumors
Neuroendocrine Tumors
 Conclusion
 References
 
Differentiated Thyroid Carcinoma
Radioiodine scintigraphy is widely used in the management of patients with differentiated thyroid carcinoma to identify residual, recurrent, or metastatic tumor. Although whole-body 123I and 131I scintigraphy are highly sensitive, normal physiologic uptake reduces the specificity of planar imaging, and the lack of anatomic landmarks can make interpretation difficult. Hybrid imaging with SPECT-CT enables precise anatomic localization of tracer uptake, which improves specificity by differentiating pathologic (Fig. 3A, 3B) from physiologic (Fig. 4A, 4B) uptake. Accurate detection of additional sites of disease will help determine suitability for surgery or radioiodine therapy [4]. In addition, SPECT-CT can also be used for more accurate dosimetry (3D volume) before radioiodine (131I) therapy [5].


Figure 5
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  		Fig. 3A —28-year-old woman with previously treated differentiated thyroid carcinoma reviewed in clinic and found to have rising thyroglobulin level. Anterior planar image from whole-body 131I scintigram shows moderately increased focus of tracer uptake in mid abdomen (arrow). Note physiologic uptake in salivary glands (SG), stomach (St), and colon (GI).

 

Figure 6
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  		Fig. 3B —28-year-old woman with previously treated differentiated thyroid carcinoma reviewed in clinic and found to have rising thyroglobulin level. Fused axial (top) and sagittal (bottom) SPECT-CT images localize focus of uptake to right side of L2 vertebral body (arrow). Corresponding low-dose CT images showed lytic lesion at this site, which is consistent with bone metastasis (not shown). Patient underwent further treatment with radioactive iodine.

 

Figure 7
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  		Fig. 4A —34-year-old woman with papillary thyroid carcinoma who was recently treated with radioactive iodine. Anterior planar image from postablation whole-body 131I scintigram shows intense tracer uptake in residual thyroid tissue in neck. Note additional focus of increased uptake in right hemipelvis (arrow), which was believed to be suspicious for a metastatic lesion.

 

Figure 8
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  		Fig. 4B —34-year-old woman with papillary thyroid carcinoma who was recently treated with radioactive iodine. Fused axial (left) and coronal (right) SPECT-CT images localize tracer uptake in right hemipelvis to cecum (arrow). This was due to physiologic bowel excretion and avoided a potential false-positive interpretation.

 
Poorly Differentiated Thyroid Tumors
Although differentiated thyroid carcinomas have a good prognosis, dedifferentiated tumors are much more aggressive and are associated with a poorer prognosis. These tumors lose the ability to concentrate iodine, making detection and patient management more challenging. Fluorine-18 FDG PET/CT has emerged as a more sensitive and specific technique than radioiodine scintigraphy in the assessment of dedifferentiated thyroid carcinomas [6]. At present, limited availability and greater cost have delayed widespread implementation in this setting. However, SPECT-CT can be used with a combination of radio-pharmaceuticals, including 111In pentreotide, 201Tl chloride, and 99mTc-MIBI to improve the detection and localization of poorly differentiated tumors (Fig. 5A, 5B).


Figure 9
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  		Fig. 5A —67-year-old man with previously treated differentiated thyroid carcinoma and markedly raised thyroglobulin level. Whole-body iodine scintigraphy was negative. Anterior planar scintigram obtained 24 hours after administration of 111In-pentreotide shows intense uptake in right upper thorax (curved arrow), lower grade uptake in left hemithorax (arrowhead) and right shoulder region (straight arrow).

 

Figure 10
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  		Fig. 5B —67-year-old man with previously treated differentiated thyroid carcinoma and markedly raised thyroglobulin level. Whole-body iodine scintigraphy was negative. Fused axial SPECT-CT image (top right) and corresponding low-dose CT image (lung windows) (top left) localize uptake in thorax to bilateral lung metastases (arrows). Fused axial SPECT-CT image (bottom right) and corresponding image from low-dose CT (bone windows) (bottom left) localize tracer accumulation in right shoulder to bone metastasis in right scapula (arrowheads). Large focus of uptake in right upper chest was due to mediastinal nodal metastasis (not shown).

 
Medullary Thyroid Carcinoma
Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor that accounts for up to 10% of thyroid neoplasms. Cross-sectional imaging using sonography, CT, and MRI is used to stage patients before surgery. Functional imaging using radioiodine-labeled metaiodobenzylguanidine (MIBG) scintigraphy is often complementary. Use of hybrid SPECT-CT improves the accuracy of staging (Fig. 6A, 6B) and has a valuable role in the assessment of patients with suspected recurrence (Fig. 7A, 7B). MTC is most commonly sporadic, but approximately 25% of cases are associated with multiple endocrine neoplasia (MEN) syndrome type II. In these patients, MTC is more aggressive, often with bilateral and multicentric disease. Accurate staging is essential before surgery, particularly because patients may also have a pheochromocytoma that could lead to fatal complications if unrecognized (Fig. 6A, 6B).


Figure 11
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  		Fig. 6A —42-year-old man with medullary thyroid carcinoma and family history of multiple endocrine neoplasia (MEN) type IIa. Anterior planar image from 123I MIBG (metaiodobenzylguanidine) scintigram shows focal uptake in left side of neck consistent with known medullary thyroid carcinoma (large arrow) with more subtle focus in left upper neck (small arrow). In addition, note bilateral tracer uptake in upper abdomen (arrowheads), consistent with bilateral pheochromocytomas, which were confirmed on subsequent staging CT (not shown).

 

Figure 12
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  		Fig. 6B —42-year-old man with medullary thyroid carcinoma and family history of multiple endocrine neoplasia (MEN) type IIa. Axial low dose CT image (top) and fused SPECT-CT image (bottom) in same patient localizes uptake in left upper neck to nonpathologically enlarged cervical lymph node (arrows). Nodal metastasis was confirmed at surgery.

 

Figure 13
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  		Fig. 7A —54-year-old woman with previously treated medullary thyroid carcinoma and rising calcitonin level. Cross-sectional imaging was unremarkable. Anterior planar image from whole-body 123I MIBG scintigram shows low-grade focus of tracer uptake in left side of neck (arrow).

 

Figure 14
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  		Fig. 7B —54-year-old woman with previously treated medullary thyroid carcinoma and rising calcitonin level. Cross-sectional imaging was unremarkable. Fused axial (left) and coronal (right) SPECT-CT images localize abnormal uptake to left thyroid bed (arrows), suspicious for recurrent disease. This was confirmed at surgery.

 

Neuroendocrine Tumors
Top
 Abstract
 Introduction
 Parathyroid Tumors
 Thyroid Tumors
 Neuroendocrine Tumors
Conclusion
 References
 
Neuroendocrine tumors (NET) are a diverse group of neoplasms that can be broadly divided into gastroenteropancreatic (GEP) and neural crest tumors. The former group can be further subdivided into gastrointestinal carcinoids (foregut, midgut, and hindgut) and pancreatic islet cell tumors (insulinomas and VIPomas [vasoactive intestinal polypeptide tumors]). The neural crest tumors include pheochromocytomas, paragangliomas, neuroblastomas, and ectopic ACTH-secreting tumors.

Gastroenteropancreatic Tumors
Management of these neoplasms is broadly based on surgical excision of primary and solitary metastatic tumors or chemotherapy for more widespread disease. Staging using conventional imaging is often difficult because of the small size of primary tumors. Somatostatin-receptor scintigraphy (SRS) using 111In pentreotide is superior to conventional anatomic imaging for detection of gastroenteropancreatic tumors, with a sensitivity and specificity of 90% and 80%, respectively [7]. This technique is widely used as an adjunct to cross-sectional imaging for initial staging, detection of recurrence, and assessing response to therapy [8, 9].

SRS is hampered by poor anatomic localization, normal physiologic excretion, and benign uptake in conditions such as Graves' disease, accessory splenic tissue, and granulomatous lung disease, which reduces specificity. Hybrid imaging using SPECT-CT allows more precise anatomic delineation (Figs. 8A, 8B and 9A, 9B), detection of additional sites of disease (Figs. 10A, 10B and 11A, 11B), and improved specificity by exclusion of false-positive uptake at sites of physiologic tracer activity (Fig. 12A, 12B). SPECT-CT has a proven incremental value in image interpretation and a positive effect on the management of patients with neuroendocrine tumors [10].


Figure 15
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  		Fig. 8A —74-year-old man with previously resected midgut carcinoid tumor and rising tumor markers (chromogranin-A). Anterior planar scintigram obtained 24 hours after administration of 111In pentreotide shows intense focus of tracer uptake in thorax (arrow). Note physiologic uptake in liver, spleen, kidneys, and bladder.

 

Figure 16
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  		Fig. 8B —74-year-old man with previously resected midgut carcinoid tumor and rising tumor markers (chromogranin-A). Fused axial (top) and sagittal (bottom) SPECT-CT images localize abnormal tracer uptake to anterior wall of right ventricle (arrows). Subsequent cardiac MRI confirmed that this represented an intracardiac metastasis. This is a rare but recognized site of metastatic disease. SPECT-CT was instrumental in accurately localizing anatomic site of disease.

 

Figure 17
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  		Fig. 9A —32-year-old man with suspected gastrinoma that had evaded detection on conventional imaging. Anterior planar scintigram obtained 24 hours after administration of 111In pentreotide shows abnormal focus of tracer uptake in midline of upper abdomen (arrow).

 

Figure 18
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  		Fig. 9B —32-year-old man with suspected gastrinoma that had evaded detection on conventional imaging. Axial SPECT (top), low-dose CT (middle), and fused SPECT-CT (bottom) images localize focal uptake to mid body of pancreas (crosshairs), consistent with pancreatic neuroendocrine tumor. Gastrinoma was confirmed after surgical excision. SPECT-CT was instrumental in preoperative planning in this case.

 

Figure 19
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  		Fig. 10A —59-year-old man with bronchial carcinoid tumor and extensive liver metastasis who was being considered for hepatic chemoembolization. Anterior planar scintigram obtained 24 hours after administration of 111In pentreotide shows multiple foci of increased tracer uptake in liver, consistent with known liver metastases. In addition, a subtle focal area of uptake is present in left pelvis (arrow).

 

Figure 20
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  		Fig. 10B —59-year-old man with bronchial carcinoid tumor and extensive liver metastasis who was being considered for hepatic chemoembolization. Fused axial (left) and coronal (right) SPECT-CT images localize pelvic uptake to occult left ischial bone metastasis (arrows). Note physiologic tracer activity in bladder on fused coronal image. In view of the extrahepatic disease, patient instead underwent systemic radionuclide therapy.

 

Figure 21
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  		Fig. 11A —72-year-old woman with metastatic pancreatic neuroendocrine tumor (VIPoma [vasoactive intestinal polypeptide tumor]) who was being considered for radionuclide therapy. Anterior planar scintigram obtained 24 hours after administration of 111In pentreotide shows multifocal uptake in liver from known metastases. Note adjacent tubular uptake extending to midline (large arrow). In addition, more subtle focal uptake is shown in right upper thorax (small arrow).

 

Figure 22
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  		Fig. 11B —72-year-old woman with metastatic pancreatic neuroendocrine tumor (VIPoma [vasoactive intestinal polypeptide tumor]) who was being considered for radionuclide therapy. Fused multiplanar images from SPECT-CT (top and middle) localize focal uptake in upper thorax to right second rib (curved arrow). Corresponding axial CT image on bone windows (bottom) shows cortical destruction (arrowhead), consistent with bone metastasis. Up to 30–40% of neuroendocrine metastasis are not visualized with conventional imaging techniques. Coronal SPECT-CT image shows tracer uptake from multiple liver metastases and portal vein tumor thrombus (straight arrow) that was subsequently confirmed on MRI (not shown).

 

Figure 23
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  		Fig. 12A —78-year-old man with previously treated midgut carcinoid tumor and slightly elevated tumor markers. Anterior planar scintigram obtained 24 hours after administration of 111In pentreotide shows focal uptake in left upper quadrant of abdomen that is suspicious for metastatic disease (arrow). Note physiologic tracer uptake in liver, kidneys, and bladder.

 

Figure 24
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  		Fig. 12B —78-year-old man with previously treated midgut carcinoid tumor and slightly elevated tumor markers. Fused axial SPECT-CT (top) and contrast-enhanced CT (bottom) images show focal uptake in left upper quadrant is physiologic and due to a spleniculus (arrows). SPECT-CT was important in this case in preventing false-positive interpretation.

 
Neural Crest Tumors
Pheochromocytoma is a functional tumor derived from the catecholamine-secreting chromaffin cells of the adrenal medulla. Occasionally, tumors can be extraadrenal, located anywhere in the sympathetic system from the neck to the pelvis (10% of adults and 30% of children). Ten percent of tumors are malignant with a high incidence of metastatic disease at presentation. Pheochromocytomas may be associated with inherited syndromes, such as neurofibromatosis, von-Hippel Lindau syndrome, or MEN type II, and with syndromic tumors more often bilateral (Fig. 6A, 6B). Cross-sectional imaging has high sensitivity for the detection of adrenal tumors [11]. MIBG scintigraphy is used for functional characterization of equivocal CT lesions, detection of extraadrenal tumors, and occult metastases (Fig. 13A, 13B). Accurate assessment of additional sites of disease directly affects patient management and guides suitability for surgical resection or therapeutic 131I MIBG therapy [9]. SPECT-CT allows more accurate anatomic localization of focal areas of avid MIBG uptake (Figs. 6A, 6B and 13A, 13B) and exclusion of normal physiologic uptake or excretion.


Figure 25
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  		Fig. 13A —67-year-old man with malignant pheochromocytoma after adrenalectomy and resection of lung metastasis. Anterior planar scintigram obtained 24 hours after administration of 123I MIBG (metaiodobenzylguanidine) shows focal uptake in left skull (large arrow) and right mediastinum (small arrow). Note physiologic tracer uptake in salivary glands, lung, liver, bowel, and renal tract. Whether skull activity was artifactual due to skin contamination was unclear.

 

Figure 26
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  		Fig. 13B —67-year-old man with malignant pheochromocytoma after adrenalectomy and resection of lung metastasis. Fused axial (left) and coronal (right) SPECT-CT images show that left scalp uptake is in skull vault, consistent with bone metastasis (arrows). Right-sided thoracic uptake was localized to enlarged right hilar nodes (not shown). Patient subsequently underwent MIBG-labeled radionuclide therapy.

 
Neuroblastomas account for 10% of pediatric tumors and can arise anywhere along the sympathetic chain, the most common site being the adrenal gland. Accurate staging is essential to guide management. Low-stage disease is treated surgically, although patients with more advanced disease undergo chemotherapy and radionuclide therapy. Initial imaging with CT or MRI is used to assess the primary tumor and potential resectability. MIBG scintigraphy is often complementary for disease staging, assessment of response to treatment, and detection of disease recurrence. SPECT-CT improves localization of tumor sites, especially adjacent to organs with physiologic MIBG uptake, such as the heart, liver, and renal tract, and thus has a direct impact on staging disease. Likewise, accurate detection and localization of neuroblastoma recurrence may help guide surgical excision of isolated disease (Fig. 14A, 14B).


Figure 27
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  		Fig. 14A —3-year-old boy with previously treated neuroblastoma. Planar images on routine surveillance MIBG (metaiodobenzylguanidine) scan showed low grade focal uptake in right upper thorax. (Courtesy of Bradley KM, Oxford, UK) Multiplanar images from 123I-MIBG SPECT-CT acquisition localize focal uptake to supraclavicular fossa (crosshairs).

 

Figure 28
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  		Fig. 14B —3-year-old boy with previously treated neuroblastoma. Planar images on routine surveillance MIBG (metaiodobenzylguanidine) scan showed low grade focal uptake in right upper thorax. (Courtesy of Bradley KM, Oxford, UK) Coronal T2-weighted image from subsequent MRI of right upper chest confirmed a minimally enlarged lymph node in the right supraclavicular fossa (arrow). This was resected and confirmed to be due to recurrent neuroblastoma.

 

Conclusion
Top
 Abstract
 Introduction
 Parathyroid Tumors
 Thyroid Tumors
 Neuroendocrine Tumors
 Conclusion
References
 
Combined anatomic and functional imaging using hybrid SPECT-CT is of incremental value in the assessment of selected patients with endocrine neoplasms. It has a valuable role in the accurate localization of primary tumor sites and improved detection of metastatic and recurrent disease. The technique has a proven impact on patient management in a variety of settings.


Acknowledgments
 
We thank K. M. Bradley, consultant radiologist and nuclear medicine physician, Oxford Radcliffe Hospitals NHS Trust, Oxford, UK, for providing the images in Fig. 14A, 14B.


References
Top
 Abstract
 Introduction
 Parathyroid Tumors
 Thyroid Tumors
 Neuroendocrine Tumors
 Conclusion
 References
 

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  2. Krausz MD, Bettman L, Guralnik L, et al. Technetium-99m-MIBI SPECT/CT in primary hyperparathyroidism. World J Surg2006; 30:76 –83[CrossRef][Medline]
  3. Krausz Y, Israel O. Single-photon emission computed tomography/computed tomography in endocrinology. Semin Nucl Med 2006; 36:267 –274[CrossRef][Medline]
  4. Yamamoto Y, Nishiyama Y, Monden T, et al. Clinical usefulness of fusion of 131I SPECT and CT images in patients with differentiated thyroid carcinoma. J Nucl Med 2003;44 :1905 –1910[Abstract/Free Full Text]
  5. Prideaux AR, Song H, Hobbs RF, et al. Three-dimensional radiobiologic dosimetry: application of radiobiologic modeling to patient-specific 3-dimensional imaging-based internal dosimetry. J Nucl Med 2007; 48:1008 –1016[Abstract/Free Full Text]
  6. AL-Nahhas A. Dedifferentiated thyroid carcinoma: the imaging role of 18F-FDG PET and noniodine radiopharmaceuticals. Nucl Med Comm 2004; 25:891 –895[CrossRef][Medline]
  7. Pfannenberg AC, Eschmann SM, Morger M, et al. Benefit of anatomical–functional image fusion in the diagnostic work-up of neuroendocrine neoplasms. Eur J Nucl Med Mol Imaging2003; 30:835 –843[Medline]
  8. Krausz Y, Keidar Z, Kogan I, et al. SPECT/CT hybrid imaging with 111In-pentetreotide in assessment of neuroendocrine tumours. Clin Endocr 2003;59 : 565–573[CrossRef][Medline]
  9. Rufini V, Calcagni ML, Baum RP. Imaging of neuroendocrine tumours. Semin Nucl Med 2006;36 : 228–247[CrossRef][Medline]
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