Clinical Utility of Hybrid SPECT-CT in Endocrine Neoplasia
Abstract
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.
Introduction
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
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.
Thyroid Tumors
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].
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).
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).
Neuroendocrine Tumors
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].
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.
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).
Conclusion
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
Footnotes
Address correspondence to C. N. Patel ([email protected]).
CME
This article is available for CME credit.
See www.arrs.org for more information.
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History
Submitted: July 26, 2007
Accepted: September 13, 2007
First published: November 23, 2012
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