¹³¹I-Metaiodobenzylguanidine Theranostics in Neuroblastoma: Historical Perspectives; Practical Applications.

Much efficacy is gained in clinical practice if a single agent can be used for both diagnosis and therapy, a practice termed theranostics. Metaiodobenzylguanidine (mIBG), a norepinephrine analogue with high sensitivity and specificity for neuroblastoma, is an exemplar of theranostics. The physiologic biodistribution of mIBG, with absence of uptake in bone and bone marrow, allows ready detection not only of primary soft tissue tumors but also of disease in bone and marrow, the two most common sites of metastases in those with neuroblastoma. Owing to its increased sensitivity and specificity in disease detection compared to the Technetium-99m methylene diphosphonate bone scan, (123)I-mIBG has become the cornerstone of staging and therapeutic response monitoring in patients with neuroblastoma. More recently, semiquantitative scoring systems have been developed to evaluate disease burden and response to treatment based on (123)I-mIBG scans. Initial data suggest that the use of these semiquantitative scoring methods has prognostic value in assessing outcomes for patients with high-risk neuroblastoma. When labeled with (131)I, mIBG can be used as a systemic therapeutic agent to treat high-risk disease, and to date, over 1000 patients with neuroblastoma have been treated worldwide with this agent. This article reviews the evolution of (131)I-mIBG therapy from its initial use as a single therapeutic agent to modern applications involving high-dose chemotherapy and autologous stem-cell transplant as well as its use as a front-line agent in high-risk neuroblastoma.

Management of Differentiated Thyroid Cancer in Children: Focus on the American Thyroid Association Pediatric Guidelines.

First introduced in 1946, radioactive iodine (I-131) produces short-range beta radiation with a half-life of 8 days. The physical properties of I-131 combined with the high degree of uptake in the differentiated thyroid cancers (DTCs) led to the use of I-131 as a therapeutic agent for DTC in adults. There are two indications for the potential use of I-131 therapy in pediatric thyroid disorders: nonsurgical treatment of hyperthyroidism owing to Graves' disease and the treatment of children with intermediate- and high-risk DTC. However, children are not just miniature adults. Not only are children and the pediatric thyroid gland more sensitive to radiation than adults but also the biologic behavior of DTC differs between children and adults as well. As opposed to adults, children with DTC typically present with advanced disease at diagnosis; yet, they respond rapidly to therapy and have an excellent prognosis that is significantly better than that in adult counterparts with advanced disease. Unfortunately, there are also higher rates of local and distant disease recurrence in children with DTC compared with adults, mandating lifelong surveillance. Further, children have a longer life expectancy during which the adverse effects of I-131 therapy may become manifest. Recognizing the differences between adults and children with DTC, the American Thyroid Association commissioned a task force of experts who developed and recently published a guideline to address the unique issues related to the management of thyroid nodules and DTC in children. This article reviews the epidemiology, diagnosis, staging, treatment, therapy-related effects, and suggestions for surveillance in children with DTC, focusing not only on the differences between adults and children with this disease but also on the latest recommendations from the inaugural pediatric management guidelines of the American Thyroid Association.

Semiquantitative analysis of hypothalamic damage on MRI predicts risk for hypothalamic obesity.

OBJECTIVE: Excessive weight gain frequently occurs in patients with hypothalamic tumors and lesions leading to hypothalamic obesity (HO). METHODS: Digital brain magnetic resonance imaging (MRI) and clinical outcomes were studied retrospectively in a single center, including 45 children with postoperative lesions in the sellar region (41 craniopharyngiomas, 4 with Rathke's cleft cysts), ∼5 years post-surgery, mean age 13.9 years. Four standard sections covering hypothalamic areas critical to energy homeostasis were used to assess lesions and calculate a hypothalamic lesion score (HLS); the association with HO was examined. RESULTS: Compared to subjects who did not develop HO (n = 23), subjects with HO (n = 22) showed more frequently lesions affecting the third ventricular floor, mammillary bodies, and anterior, medial (all P < 0.05), and most importantly posterior hypothalamus (P < 0.01). The HLS correlated significantly with BMI z-score changes 12 and 30 months post-surgery, even after adjusting for potential confounders of gender, age at surgery, surgery date, surgery BMI z-score, hydrocephalus, and residual hypothalamic tumor (r = 0.34, P = 0.03; r = 0.40, P = 0.02, respectively). Diabetes insipidus was found to be an endocrine marker for HO risk. CONCLUSIONS: The extent of damage following surgery in the sellar region can be assessed by MRI using a novel scoring system for early HO risk assessment.

Efficacy of cabazitaxel in mouse models of pediatric brain tumors.

BACKGROUND: There is an unmet need in the treatment of pediatric brain tumors for chemotherapy that is efficacious, avoids damage to the developing brain, and crosses the blood-brain barrier. These experiments evaluated the efficacy of cabazitaxel in mouse models of pediatric brain tumors. METHODS: The antitumor activity of cabazitaxel and docetaxel were compared in flank and orthotopic xenograft models of patient-derived atypical teratoid rhabdoid tumor (ATRT), medulloblastoma, and central nervous system primitive neuroectodermal tumor (CNS-PNET). Efficacy of cabazitaxel and docetaxel were also assessed in the Smo/Smo spontaneous mouse medulloblastoma tumor model. RESULTS: This study observed significant tumor growth inhibition in pediatric patient-derived flank xenograft tumor models of ATRT, medulloblastoma, and CNS-PNET after treatment with either cabazitaxel or docetaxel. Cabazitaxel, but not docetaxel, treatment resulted in sustained tumor growth inhibition in the ATRT and medulloblastoma flank xenograft models. Patient-derived orthotopic xenograft models of ATRT, medulloblastoma, and CNS-PNET showed significantly improved survival with treatment of cabazitaxel. CONCLUSION: These data support further testing of cabazitaxel as a therapy for treating human pediatric brain tumors.

Radionuclide shunt patency study for suspected ventriculoatrial shunt malfunction.

OBJECTIVE: Radionuclide shunt studies have been used for decades to evaluate intracranial shunt patency (SP); however, the methodology is neither standardized nor well validated. The purpose of this study was to determine the clinical utility of radionuclide ventriculoatrial (VA) SP study for diagnosis of suspected shunt malfunction. METHODS: A retrospective review was undertaken of all patients who had a VA radionuclide SP study between 2001 and 2009. All had a 20-minute gamma camera acquisition (1 min/frame) immediately following injection of 99mTc DTPA into the shunt reservoir. Time-activity curves were generated and a half-time (T½) of emptying quantified. The results were correlated with the final clinical diagnoses. RESULTS: Forty-nine studies in 40 adult patients with a minimum of 6 months' follow-up were analyzed. Thirteen shunt studies had a T½ of 3.9 to 8.0 minutes, had final diagnosis of normal functioning shunt, and did not need revision surgery for a mean follow-up of 15.1 months. Fourteen patient studies had a T½ of less than 3.9 minutes; 13 had final diagnosis of overdraining shunts, and 1 required revision surgery. Twenty-two had a T½ longer than 8 minutes: 13 had final diagnosis of shunt obstruction, 4 had overdrainage, and 5 had underdrainage. CONCLUSIONS: The radionuclide SP study is valuable for evaluation of VA SP. Results can be interpreted using a single variable (T½). T½ of 3.9 to 8 minutes indicates a patent shunt; T½ less than 3.9 minutes is consistent with overdrainage. T½ of >8 requires further evaluation to differentiate between obstruction and overdrainage/underdrainage.

The Roles of Fluorodeoxyglucose-PET/Computed Tomography in Ovarian Cancer: Diagnosis, Assessing Response, and Detecting Recurrence.

The potential roles of fluorodeoxyglucose positron emission tomography/computed tomography imaging in ovarian cancer include noninvasive characterization of an ovarian mass, staging, and treatment planning. This article assesses these roles for predicting and monitoring response to treatment, restaging, and early diagnosis of recurrence.

Imaging of the pediatric airway.

Airway compromise can be fixed, dynamic (with varying degrees of collapse during the respiratory cycle), or exhibit both components. The location of the abnormality can be classified as extrinsic (located outside but exerting mass effect on the airway) or intrinsic (intramural and/or intraluminal). The etiologies of airway compromise are categorized as: congenital, infectious, inflammatory, traumatic, vascular, or neoplastic (1). The role of imaging of the airway is to determine the presence, nature and anatomic level of airway compromise, categorize it as intrinsic or extrinsic, provide a differential diagnosis, and guide further imaging or management (1). The differential diagnosis of a lesion takes into account the patient's age and gender, location of the lesion, clinical presentation, and imaging appearance.

Osteoblastic bone flare on F18-FDG PET in non-small cell lung cancer (NSCLC) patients receiving bevacizumab in addition to standard chemotherapy.

Positron emission tomography (PET) is used routinely to follow therapeutic response in patients treated for non-small cell lung cancer (NSCLC). In responding patients it is generally expected that the observed decrease in fluorodeoxyglucose uptake should be similar in all lesions. In other disease entities though, isolated cases have been documented of asynchronous increases in activity in metastatic bone lesions ("bone flare") despite evidence of therapeutic response or stability in other lesions. Here, we describe four NSCLC cases in which the results of interim PET scans were misleading due to osteoblastic flare phenomenon. In all four cases, patients were treated with bevacizumab in addition to standard chemotherapy. All four patients developed isolated worsening of their skeletal metastases on PET/CT (computed tomography) analysis (increase in fluorodeoxyglucose activity) despite apparent response or stable disease elsewhere. Subsequent scans confirmed that the "worsening" was transient, consistent with a flare response. Awareness of the phenomena is important for physicians treating NSCLC patients, particularly with bevacizumab.

PET/CT imaging of gastrointestinal stromal tumor with calcified peritoneal implants after imatinib therapy.

Calcified tumor mass is an unusual feature of gastrointestinal stromal tumor (GIST) at initial presentation. However, it may develop after imatinib therapy and be erroneously attributed to a second primary malignancy. A 56-year-old woman with a 4.5-year history of metastatic GIST presented to our institution for PET/CT imaging at baseline and at 3 and 15 months after imatinib therapy. Serial PET/CT images demonstrated increasing calcification in peritoneal implants on CT and increasing FDG activity.

Parathyroid scintigraphy in patients with primary hyperparathyroidism: 99mTc sestamibi SPECT and SPECT/CT.

The clinical diagnosis of primary hyperparathyroidism is based largely on serum laboratory test results, as patients often are asymptomatic. Surgery, often with bilateral exploration of the neck, has been considered the definitive treatment for symptomatic disease. However, given that approximately 90% of cases are due to a single parathyroid adenoma, a better treatment may be the selective surgical excision of the hyperfunctioning parathyroid gland after its preoperative identification and localization at radiologic imaging. Scintigraphy and ultrasonography are the imaging modalities most often used for preoperative localization. Various scintigraphic protocols may be used in the clinical setting: Single-phase dual-isotope subtraction imaging, dual-phase single-isotope imaging, or a combination of the two may be used to obtain planar or tomographic views. Single photon emission computed tomography (SPECT) with the use of technetium-99m ((99m)Tc) sestamibi as the radiotracer, especially when combined with x-ray-based computed tomography (CT), is particularly helpful for preoperative localization: The three-dimensional functional information from SPECT is fused with the anatomic information obtained from CT. In addition, knowledge of the anatomy and embryologic development of the parathyroid glands and the pathophysiology of primary hyperparathyroidism aid in the identification and localization of hyperfunctioning glands.