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Abstract Background Neuroblastoma is the most common extra-cranial pediatric solid tumor. 131I-metaiodobenzylguanidine (MIBG) is a targeted radiopharmaceutical highly specific for neuroblastoma tumors, providing potent radiotherapy to widely metastatic disease. Aurora kinase A (AURKA) plays a role in mitosis and stabilization of the MYCN protein in neuroblastoma. We aimed to study the impact of AURKA inhibitors on DNA damage and tumor cell death in combination with 131I-MIBG therapy in a pre-clinical model of high-risk neuroblastoma. Results Using an in vivo model of high-risk neuroblastoma, we demonstrated a marked combinatorial effect of 131I-MIBG and alisertib on tumor growth. In MYCN amplified cell lines, the combination of radiation and an AURKA A inhibitor increased DNA damage and apoptosis and decreased MYCN protein levels. Conclusion The combination of AURKA inhibition with 131I-MIBG treatment is active in resistant neuroblastoma models.

Meta-iodobenzylguanidine (MIBG) is used as a chemical precursor of radioiodinated (123I or 131I) MIBG preparation. In order to control the quality of MIBG, in this study, Infrared identification of self-made MIBG was carried out, the physical and chemical properties of solubility, pH, melting point and drying weight loss were determined, the content of elemental impurities was determined by ICP-MS, the headspace gas chromatography of residual solvent was established, and the content and related substances were determined by HPLC were established. The results for multiple batches of MIBG analysis showed that they met the requirements for medicinal precursors, the infrared spectrum of MIBG was consistent with that of the reference substance, the pH was in the range of 4.0-6.0, the melting point was 167-170 ℃, and the drying weight loss was less than 0.3%; ethanol residue was less than 0.5%, the content of elemental impurities was lower than the control threshold, together with no related impurities detected, and the contents of MIBG were 98.0%-102.0%. The quality standard of MIBG established in this study provides and provided basis for the quality control of MIBG.

Heart failure (HF) with preserved left ventricular ejection fraction (LVEF) is a heterogeneous syndrome. An LVEF of 50% is widely used to categorize patients with HF; however, this is controversial. Previously, we have reported that patients with an LVEF of ≥ 58% have good prognoses. Further, cardiac sympathetic nervous system (SNS) activation is a feature of HF. In this retrospective, observational study, the cardiac SNS activity of HF patients (n = 63, age: 78.4 ± 9.6 years; male 49.2%) with LVEF ≥ 58% (n = 15) and LVEF < 58% (n = 48) were compared using 123I-metaiodobenzylguanidine scintigraphy. During the follow-up period (median, 3.0 years), 18 all-cause deaths occurred. The delayed heart/mediastinum (H/M) ratio was significantly higher in the LVEF ≥ 58% group than in the LVEF < 58% group (2.1 ± 0.3 vs. 1.7 ± 0.4, p = 0.004), and all-cause mortality was significantly lower in patients in the former than those in the latter group (log-rank, p = 0.04). However, when these patients were divided into LVEF ≥ 50% (n = 22) and LVEF < 50% (n = 41) groups, no significant differences were found in the delayed H/M ratio, and the all-cause mortality did not differ between the groups (log-rank, p = 0.09). In conclusion, an LVEF of 58% is suitable for reclassifying patients with HF according to cardiac SNS activity.

Abstract Background Parkinson’s disease (PD) patients often suffer from cardiac sympathetic denervation, a hallmark of which is orthostatic hypotension. Denervation supersensitivity to sympathomimetic drugs is also seen in such patients, and this phenomenon is important and can be sometimes dangerous. Case presentation A 65-year-old male underwent gastrojejunostomy. The patient had severe PD and did not exhibit metaiodobenzylguanidine (MIBG) accumulation in his heart, which was indicative of cardiac sympathetic nerve denervation. When 8 mg of ephedrine was administered intravenously, an unexpectedly large increase in blood pressure was observed. The phenomenon recurred when 4 mg of ephedrine was administered again, and nicardipine was required to suppress the patient’s blood pressure. Conclusions Denervation supersensitivity is not as well recognized as other complications seen in PD patients, but anesthesiologists should be aware of it because sympathomimetic drugs can have excessively strong effects in patients with the condition.

Background: 18-Fluorodeoxyglucose positron emission tomography (FDG-PET) has established a role in the evaluation of several malignancies. However, its precise clinical role in the neural crest cell tumors continues to evolve. Purpose: The purpose of this study was to compare iodine-131 metaiodobenzylguanidine (131I-MIBG) and FDG-PET of head to head in patients with neural crest tumors both qualitatively and semiquantitatively and to determine their clinical utility in disease status evaluation and further management. Materials and Methods: A total of 32 patients who had undergone 131I-MIBG and FDG-PET prospectively were evaluated and clinicopathologically grouped into three categories: neuroblastoma, pheochromocytoma, and medullary carcinoma thyroid. Results: In 18 patients of neuroblastoma, FDG PET and 131I-MIBG showed patient-specific sensitivity of 84% and 72%, respectively. The mean maximum standardized uptake value (SUVmax) of primary lesions in patients with unfavorable histology was found to be relatively higher than those with favorable histology (5.18 ± 2.38 vs. 3.21 ± 1.69). The mean SUVmaxof two common sites (posterior superior iliac spine [PSIS] and greater trochanter) was higher in patients with involved marrow than those with uninvolved one (2.36 and 2.75 vs. 1.26 and 1.34, respectively). The ratio of SUVmaxof the involved/contralateral normal sites was 2.16 ± 1.9. In equivocal bone marrow results, the uptake pattern with SUV estimation can depict metastatic involvement and help in redirecting the biopsy site. Among seven patients of pheochromocytoma, FDG-PET revealed 100% patient-specific sensitivity. FDG-PET detected more metastatic foci than 131I-MIBG (18 vs. 13 sites). In seven patients of medullary carcinoma thyroid, FDG-PET localized residual, recurrent, or metastatic disease with much higher sensitivity (32 metastatic foci with 72% patient specific sensitivity) than 131I-MIBG, trending along the higher serum calcitonin levels. Conclusions: FDG-PET is not only a good complementary modality in the management of neural crest cell tumors but also it can even be superior, especially in cases of 131I-MIBG nonavid tumors.

Neuroblastoma is the third common tumor in children. Imaging plays an important role in the diagnosis, staging, treatment planning, response evaluation and in follow-up of a case of Neuroblastoma. The International Neuroblastoma Risk Group task force has recently introduced an imaging-based staging system and laid down guidelines for uniform reporting of imaging studies. This review is an update on imaging in neuroblastoma, with emphasis on these guidelines.

Pheochromocytomas are rare catecholamine-secreting tumors that arise from chromaffin tissue within the adrenal medulla and extra-adrenal sites. Due to the excess secretion of hormones, these tumors often cause debilitating symptoms and a poor quality-of-life. Although medical management plays a significant role in the treatment of pheochromocytoma patients, surgical excision remains the only cure. Pheochromocytoma usually has three classic symptoms-headache, sweating and heart palpitations (a fast heart beat) in association with markedly elevated blood pressure (hypertension). Hormones such as catecholamines and metanephrines are measured in a 24 h urine collection and metanephrines may also be measured in the blood, to make a diagnosis of pheochromocytoma. If these are greater than 2 times the normal level, imaging studies are usually done to look at the adrenal glands. We report on three cases of pheochromocytoma, which had unusual presentation.

Aim. To evaluate sympathetic nervous system activity of the heart in patients with bronchial asthma (BA) given beta-adrenomimetics (BAM). Material and methods. 27 patients with moderate BA (13 patients in an acute phase and 14 patients in remission) treated with BAM and 13 healthy people were examined by using m I-metaiodobenzylguanidine (MIBG) myocardial planar scintigraphy and estimating the washout rate, early (15-min) and late (240-min) uptake; single-photon emission computed tomography; assessment of MIBG distribution in the left ventricular myocardium, catecholamine excretion with urine. Results. It was found that the MIBG washout rate was significantly higher in asthmatic patients especially in the acute period. The cardiac MIBG uptake was significantly lower in the group of patients with impaired cardiac sympathetic activity. More ^homogeneous myocardial MIBG uptake also occurred in the asthmatic group. Norepinephrine and epinephrine excretion was significantly higher in patients with bronchial asthma and catecholamine and MIBG excretions correlated. Conclusion. Cardiac functional sympathetic activity impairment in asthmatic patients was shown by increased MIBG washout rate and reduced myocardial MIBG uptake, more inhomogeneous substance distribution in the left ventricular myocardium and higher catecholamine excretion levels reflecting sympathetic nervous activity intensification.