Anca M. Avram

Radioiodine Scintigraphy with SPECT/CT: An Important Diagnostic Tool for Thyroid Cancer Staging and Risk Stratification

Staging and risk stratification predicate the postoperative management of thyroid cancer patients, determining not only the need for 131I therapy or alternative options (conservative management without ablation, surgical reintervention, or external-beam radiation therapy) but also the long-term follow-up strategy. This paper presents the progress made in the field of thyroid cancer imaging by application of SPECT/CT technology to radioiodine scintigraphy in both diagnostic and post-therapy settings and reviews the impact of fusion radioiodine imaging on staging, risk stratification, and clinical management of patients with thyroid cancer. In addition, this paper addresses the role of preablation radioiodine imaging and provides nuclear medicine physicians with the background knowledge required for integrating information from fusion imaging into the clinical and histopathologic risk stratification for developing an individualized treatment plan for patients with thyroid cancer.Staging and risk stratification predicate the postoperative management of thyroid cancer patients, determining not only the need for (131)I therapy or alternative options (conservative management without ablation, surgical reintervention, or external-beam radiation therapy) but also the long-term follow-up strategy. This paper presents the progress made in the field of thyroid cancer imaging by application of SPECT/CT technology to radioiodine scintigraphy in both diagnostic and post-therapy settings and reviews the impact of fusion radioiodine imaging on staging, risk stratification, and clinical management of patients with thyroid cancer. In addition, this paper addresses the role of preablation radioiodine imaging and provides nuclear medicine physicians with the background knowledge required for integrating information from fusion imaging into the clinical and histopathologic risk stratification for developing an individualized treatment plan for patients with thyroid cancer.

Radiation Safety in the Treatment of Patients with Thyroid Diseases by Radioiodine 131I: Practice Recommendations of the American Thyroid Association

BACKGROUND Radiation safety is an essential component in the treatment of patients with thyroid diseases by ¹³¹I. The American Thyroid Association created a task force to develop recommendations that would inform medical professionals about attainment of radiation safety for patients, family members, and the public. The task force was constituted so as to obtain advice, experience, and methods from relevant medical specialties and disciplines. METHODS Reviews of Nuclear Regulatory Commission regulations and International Commission on Radiological Protection [corrected] recommendations formed the basic structure of the recommendations. Members of the task force contributed both ideas and methods that are used at their respective institutions to aid groups responsible for treatments and that instruct patients and caregivers in the attainment of radiation safety. There are insufficient data on long-term outcomes to create evidence-based guidelines. RESULTS The information was used to compile delineations of radiation safety. Factors and situations that govern implementation of safety practices are cited and discussed. Examples of the development of tables to ascertain the number of hours or days (24-hour cycles) of radiation precaution appropriate for individual patients treated with ¹³¹I for hyperthyroidism and thyroid cancer have been provided. Reminders in the form of a checklist are presented to assist in assessing patients while taking into account individual circumstances that would bear on radiation safety. Information is presented to supplement the treating physicians advice to patients and caregivers on precautions to be adopted within and outside the home. CONCLUSION Recommendations, complying with Nuclear Regulatory Commission regulations and consistent with guidelines promulgated by the National Council on Radiation Protection and Measurement (NCRP-155), can help physicians and patients maintain radiation safety after treatment with ¹³¹I of patients with thyroid diseases. Both treating physicians and patients must be informed if radiation safety, an integral part of therapy with ¹³¹I, is to be attained. Based on current regulations and understanding of radiation exposures, recommendations have been made to guide physicians and patients in safe practices after treatment with radioactive iodine.

Incremental Value of Diagnostic 131I SPECT/CT Fusion Imaging in the Evaluation of Differentiated Thyroid Carcinoma

OBJECTIVE The purpose of this study was to determine the incremental value of (131)I SPECT/CT over traditional planar imaging of patients with differentiated thyroid carcinoma. MATERIALS AND METHODS Fifty-six planar and SPECT/CT scans were obtained for 53 patients. Forty-eight scans were diagnostic (131)I studies before first radioiodine therapy, four were diagnostic (131)I studies with recombinant human thyroid-stimulating hormone stimulation, and four scans were posttherapy (131)I studies. Two nuclear physicians interpreted central neck and distant activity on planar scans and reviewed SPECT/CT images to assess the incremental diagnostic value with respect to localization and characterization of focal activity and to evaluate reader confidence. One of the readers was unblinded and had access to clinical, imaging, histologic, and biochemical information. RESULTS Planar scans depicted 130 neck foci and 17 distant foci. At SPECT/CT these foci were further characterized as thyroglossal duct and thyroid bed remnant (n = 98), cervical nodal metastasis or local residual disease (n = 26), physiologic activity (n = 11), and distant metastasis (n = 12). Interobserver disagreement occurred on eight of 147 foci (5%). Because of superior lesion localization and additional anatomic information derived from the low-dose CT component, incremental diagnostic value with SPECT/CT over planar imaging was found for 70 of 147 foci (47.6%), including 53 of 130 neck foci (40.8%) and all 17 (100%) distant foci. Reader confidence increased regarding 104 of 147 foci (70.7%). CONCLUSION Iodine-131 SPECT/CT is useful for accurate evaluation of regional and distant activity in characterization of foci as residual thyroid tissue or nodal, pulmonary, or osseous metastasis. Suspected physiologic mimics of disease can be confirmed with increased reader confidence.

131I-Tositumomab Radioimmunotherapy: Initial Tumor Dose–Response Results Using 3-Dimensional Dosimetry Including Radiobiologic Modeling

For optimal treatment planning in radionuclide therapy, robust tumor dose–response correlations must be established. Here, fully 3-dimensional (3D) dosimetry was performed coupling SPECT/CT at multiple time points with Monte Carlo–based voxel-by-voxel dosimetry to examine such correlations. Methods: Twenty patients undergoing 131I-tositumomab for the treatment of refractory B-cell lymphoma volunteered for the study. Sixty tumors were imaged. Activity quantification and dosimetry were performed using previously developed 3D algorithms for SPECT reconstruction and absorbed dose estimation. Tumors were outlined on CT at multiple time points to obtain absorbed dose distributions in the presence of tumor deformation and regression. Equivalent uniform dose (EUD) was calculated to assess the biologic effects of the nonuniform absorbed dose, including the cold antibody effect. Response for correlation analysis was determined on the basis of the percentage reduction in the product of the largest perpendicular tumor diameters on CT at 2 mo. Overall response classification (as complete response, partial response, stable disease, or progressive disease) used for prediction analysis was based on criteria that included findings on PET. Results: Of the evaluated tumor-absorbed dose summary measures (mean absorbed dose, EUD, and other measures from dose-volume histogram analysis), a statistically significant correlation with response was seen only with EUD (r = 0.36 and P = 0.006 at the individual tumor level; r = 0.46 and P = 0.048 at the patient level). The median value of mean absorbed dose for stable disease, partial response, and complete response patients was 196, 346, and 342 cGy, respectively, whereas the median value of EUD for each of these categories was 170, 363, and 406 cGy, respectively. At a threshold of 200 cGy, both mean absorbed dose and EUD had a positive predictive value for responders (partial response + complete response) of 0.875 (14/16) and a negative predictive value of 1.0 (3/3). Conclusion: Improved dose–response correlations were demonstrated when EUD incorporating the cold antibody effect was used instead of the conventionally used mean tumor-absorbed dose. This work demonstrates the importance of 3D calculation and radiobiologic modeling when estimating absorbed dose for correlation with outcome.

Preablation 131-I Scans With SPECT/CT in Postoperative Thyroid Cancer Patients: What Is the Impact on Staging?

CONTEXT The utility of preablation radioiodine scans for the management of differentiated thyroid cancer remains controversial. OBJECTIVE To determine the contribution of preablation Iodine 131 (131-I) planar with single-photon emission computed tomography/computed tomography (SPECT/CT; diagnostic [Dx] scans) to differentiated thyroid cancer staging. DESIGN Prospective sequential series at university clinic. METHODS Using American Joint Committee on Cancer (AJCC) tumor, node, metastasis (TNM) staging, seventh edition 320 patients post-total thyroidectomy were initially staged based on clinical and pathology data (pTN) and then restaged after imaging (TNM). The impact of Dx scans with SPECT/CT on N and M scores, and TNM stage, was assessed in younger, age <45 years, n = 138 (43%), and older, age ≥ 45 years, n = 182 (57%) patients, with subgroup analysis for T1a and T1b tumors. RESULTS In younger patients Dx scans detected distant metastases in 5 of 138 patients (4%), and nodal metastases in 61 of 138 patients (44%), including unsuspected nodal metastases in 24 of 63 (38%) patients initially assigned pathologic (p) N0 or pNx. In older patients distant metastases were detected in 18 of 182 patients (10%), and nodal metastases in 51 of 182 patients (28%), including unsuspected nodal metastases in 26 of 108 (24%) patients initially assigned pN0 or pNx. Dx scans detected distant metastases in 2 of 49 (4%) T1a, and 3 of 67 (4.5%) T1b patients. CONCLUSIONS Dx scans detected regional metastases in 35% of patients, and distant metastases in 8% of patients. Information acquired with Dx scans changed staging in 4% of younger, and 25% of older patients. Preablation scans with SPECT/CT contribute to staging of thyroid cancer. Identification of regional and distant metastases prior to radioiodine therapy has significant potential to alter patient management.

Incremental Value of 111-In Pentetreotide SPECT/CT Fusion Imaging of Neuroendocrine Tumors

RATIONALE AND OBJECTIVES Hybrid single photon-emission computed tomographic (SPECT) and computed tomographic (CT) imaging for the investigation of neuroendocrine tumors allows the fusion of functional and anatomic information in a rapid and efficient method. The aim of this study was to assess the incremental diagnostic value of (111)In pentetreotide SPECT/CT imaging compared with traditional planar and SPECT imaging with respect to lesion localization and characterization and reader confidence. MATERIALS AND METHODS Forty-nine patients (23 male, 26 female; mean age, 56.9 years; range, 14-88 years) who underwent (111)In pentetreotide planar, SPECT, and SPECT/CT imaging were eligible for this retrospective study, including patients with suspected or confirmed carcinoid tumors (n = 24), endocrine pancreatic tumors (n = 18), medullary thyroid cancer (n = 3), paragangliomas (n = 2), and multiple endocrine neoplasia type I (n = 2). Planar and SPECT images were reviewed by two blinded readers, followed by interpretation using additional SPECT/CT images in a subsequent session. A third reader provided consensus in cases with disagreements. RESULTS In 55 of 89 lesions (61.8%), (111)In pentetreotide SPECT/CT imaging improved lesion localization compared to planar and SPECT imaging; in 25 of 89 lesions (28.1%), SPECT/CT imaging changed lesion classification. In 20 of 49 patients (40.8%) for reader 1 and 14 of 49 patients (28.6%) for reader 2, (111)In pentetreotide SPECT/CT imaging provided incremental diagnostic value, which was considered likely to affect patient management in twelve of 20 and seven of 14 patients, respectively. Increased reader confidence was found in 32 of 49 patients (65.3%) for both readers with uniformly high confidence after SPECT/CT interpretation. CONCLUSIONS Hybrid (111)In pentetreotide SPECT/CT imaging provides incremental diagnostic value and greater reader confidence over planar and SPECT imaging. This is achieved though superior lesion localization, the identification of physiologic activity, and additional anatomic information derived from the nondiagnostic CT portion of the study.

SPECT/CT Evaluation of Unusual Physiologic Radioiodine Biodistributions: Pearls and Pitfalls in Image Interpretation

Radioiodine imaging has a well-established role in depicting metastatic disease after thyroidectomy in patients with well-differentiated thyroid cancer. Uptake of radioiodine in thyroid metastases depends on expression of sodium-iodide symporter (NIS) by tumor tissues. However, because radioiodine may also accumulate in normal structures and tissues, it is important to distinguish physiologic radioiodine activity from metastatic disease. Furthermore, secretions that contain radioiodine may also simulate pathologic uptake. A spectrum of physiologic distributions, normal variants, and benign mimics of disease have been described in the literature; yet, even when armed with a comprehensive knowledge of these patterns, interpreting radiologists and nuclear physicians may still encounter diagnostic uncertainty. Single-photon emission computed tomography (SPECT) with integrated computed tomography (CT) is a novel technology that, when applied to diagnostic iodine 123 or iodine 131 ((131)I) radioiodine scintigraphy, may accurately localize and help distinguish benign mimics of disease, with the potential to alter the management plan. SPECT/CT is increasingly being used with radioiodine scintigraphy to evaluate patients with thyroid cancer and shows promise for improving imaging specificity and reducing false-positive results.

Thyroid Carcinoma Metastasis to Skull with Infringement of Brain: Treatment with Radioiodine

BACKGROUND Infringement by differentiated thyroid carcinoma on the brain is rare but, when suspected, the patient deserves special attention. A patient with an enlarging metastasis of thyroid carcinoma to the skull that was impinging on the brain illustrates diagnostic and therapeutic strategies applicable to the treatment of metastatic carcinoma. METHODS A case study was performed. Computed tomography (CT) and magnetic resonance imaging (MRI) were done, serum thyroglobulin was measured, and tumor responses to thyroxine and (131)I treatments were monitored. Tumor dosimetry, enabled by scintigraphy with (131)I employing single photon emission tomography fused with CT (SPECT-CT), was performed. RESULTS The metastasis was from a follicular variant of papillary thyroid carcinoma. During thyrotropin stimulation the tumor enlarged. The tumor decreased in volume after each of two (131)I therapies. Dosimetry indicated delivery of 1970 and 2870 cGy to the tumor and 35 and 42 cGy to the brain, respectively, in the two treatments. The patient has survived for more than 11 years since diagnosis. CONCLUSIONS A metastasis from a follicular variant of papillary carcinoma increased in volume during hypothyroidism producing more infringement on the brain. Beyond the effects of thyroxine therapy, (131)I treatments induced recession of tumor volume. In patients with metastases that concentrate (131)I, dosimetry with SPECT-CT can predict absorbed doses of radiation to the tumor and to the adjacent organs and thus lay a basis for data-based decisions on (131)I therapies. Therapy may induce prolonged survival in patients with metastases infringing on the brain.

Use of Integrated SPECT/CT Imaging for Tumor Dosimetry in I-131 Radioimmunotherapy: A Pilot Patient Study

Integrated systems combining functional (single-photon emission computed tomography; SPECT) imaging with anatomic (computed tomography; CT) imaging have the potential to greatly improve the accuracy of dose estimation in radionuclide therapy. In this article, we present the methodology for highly patient-specific tumor dosimetry by utilizing such a system and apply it to a pilot study of 4 follicular lymphoma patients treated with I-131 tositumomab. SPECT quantification included three-dimensional ordered-subset expectation-maximization reconstruction and CT-defined tumor outlines at each time point. SPECT/CT images from multiple time points were coupled to a Monte Carlo algorithm to calculate a mean tumor dose that incorporated measured changes in tumor volume. The tumor shrinkage, defined as the difference between volumes drawn on the first and last CT scan (a typical time period of 15 days) was in the range 5%-49%. The therapy-delivered mean tumor-absorbed dose was in the range 146-334 cGy. For comparison, the therapy dose was also calculated by assuming a static volume from the initial CT and was found to underestimate this dose by up to 47%. The agreement between tracer-predicted and therapy-delivered tumor-absorbed dose was in the range 7%-21%. In summary, malignant lymphomas can have dramatic tumor regression within days of treatment, and advanced imaging methods allow for a highly patient-specific tumor-dosimetry calculation that accounts for this regression.

Contemporary adrenal scintigraphy

IntroductionHigh-resolution computed tomography (CT) and magnetic resonance (MR) imaging have replaced scintigraphy as primary imaging modalities for the evaluation of adrenal diseases.DiscussionThin-slice CT, CT contrast washout studies and MR pulse sequences specifically designed to identify adrenal lipid content have radically changed the approach to anatomic imaging and provide unique insight into the physical characteristics of the adrenals. With a confirmed biochemical diagnosis, further evaluation is often unnecessary, especially in diagnostic localization of diseases of the adrenal cortex. However, despite the exquisite detail afforded by anatomy-based imaging, there are not infrequently clinical situations in which the functional insight provided by scintigraphy is crucial to identify adrenal dysfunction and to assist in localization of adrenocortical and adrenomedullary disease. The introduction of hybrid PET/CT and SPECT/CT, modalities that directly integrate anatomic and functional information, redefine the radiotracer principle in the larger context of high-resolution anatomic imaging. Instead of becoming obsolete, scintigraphy is an element of a device that combines it with CT or MR to allow a direct correlation between function and anatomy, whereby the combination creates a more powerful diagnostic tool than the separate component modalities.