Application of a tungsten apron for occupational radiation exposure in nursing care of children with neuroblastoma during 131I-meta-iodo-benzyl-guanidine therapy

The use of effective shielding materials against radiation is important among medical staff in nuclear medicine. Hence, the current study investigated the shielding effects of a commercially available tungsten apron using gamma ray measuring instruments. Further, the occupational radiation exposure of nurses during 131I-meta-iodo-benzyl-guanidine (131I-MIBG) therapy for children with high-risk neuroblastoma was evaluated. Attachable tungsten shields in commercial tungsten aprons were set on a surface-ray source with 131I, which emit gamma rays. The mean shielding rate value was 0.1 ± 0.006 for 131I. The shielding effects of tungsten and lead aprons were evaluated using a scintillation detector. The shielding effect rates of lead and tungsten aprons against 131I was 6.3% ± 0.3% and 42.1% ± 0.2% at 50 cm; 6.1% ± 0.5% and 43.3% ± 0.3% at 1 m; and 6.4% ± 0.9% and 42.6% ± 0.6% at 2 m, respectively. Next, we assessed the occupational radiation exposure during 131I-MIBG therapy (administration dose: 666 MBq/kg, median age: 4 years). The total occupational radiation exposure dose per patient care per 131I-MIBG therapy session among nurses was 0.12 ± 0.07 mSv. The average daily radiation exposure dose per patient care among nurses was 0.03 ± 0.03 mSv. Tungsten aprons had efficient shielding effects against gamma rays and would be beneficial to reduce radiation exposures per patient care per 131I-MIBG therapy session.

Descriptive and prognostic value of a computational model of metastasis in high-risk neuroblastoma

High Risk Neuroblastoma (HRNB) is the second most frequent solid tumor in children. Prognosis remains poor despite multimodal therapies. Mathematical models have been developed to describe metastasis, but their prognosis value has yet to be determined and none exists in neuroblastoma.We established such a model for HRNB relying on two coefficients: α(growth) and μ (dissemination). The model was calibrated using diagnosis values of primary tumor size, lactate dehydrogenase circulating levels (LDH) and the meta-iodo-benzyl-guanidine (mIBG) SIOPEN score from nuclear imaging, using data from 49 metastatic patients treated according to the European HR_NBL1 protocol.The model was able to accurately describe the data for both total tumor mass (LDH, R2 > 0.99) and number of visible metastasis (SIOPEN, R2 = 0.96). Statistical analysis revealed significant association of LDH with overall survival (OS, p=0.0268). However, clinical variables alone were not able to generate a Cox-based model with sufficient prognosis ability (p=0.507). The parameter μ was found to be independent of the clinical variables and positively significantly associated with OS (p = 0.0175 in multivariate analysis). Critically, addition of this novel computational biomarker to the clinical data drastically improved the performances of predictive algorithms, with a concordance index in cross-validation going from 0.755 to 0.827. The resulting signature had significant prognosis ability of OS (p=0.0353).Mechanistic modeling was able to describe pathophysiological data of metastatic HRNB and outperformed the predictive value of clinical variables. The physiological substrate underlying these results has yet to be explored, and results should be confirmed in a larger cohort.SignificanceA mechanistic mathematical model of metastasis in high risk neuroblastoma is able to describe clinical data and provides a numerical biomarker with superior predictive power of overall survival than clinical data alone.

Multidisciplinary management of a large pheochromocytoma presenting with cardiogenic shock: a case report

Background Pheochromocytoma is well-known for sudden initial presentations, particularly in younger patients. Hemodynamic instability may cause serious complications and delay a patient’s ability to undergo surgical resection. Larger tumors present a further challenge because of the risk of catecholamine release during manipulations. In the case we present, increases in systemic vascular resistance caused cardiogenic shock, and the size of the lesion prompted surgeons to veer off from their usual approach. Case presentation A 38-year-old female patient was admitted to our intensive care unit with hypertension and later cardiogenic shock. Profound systolic dysfunction (left ventricular ejection fraction of 0.12) was noted together with severely increased systemic vascular resistance, and gradually responded to vasodilator infusion. A left-sided 11-cm adrenal mass was found with computed tomography and confirmed a pheochromocytoma with a meta-iodo-benzyl-guanidine scintigraphy. Surgical treatment was carefully planned by the endocrinologist, anesthesiologist and surgeon, and was ultimately successful. After prolonged hemodynamic stabilization, open adrenalectomy and nephrectomy were deemed safer because of lesion size and the apparent invasion of the kidney. Surgery was successful and the patient was discharged home 5 days after surgery. She is free from disease at almost 2 years from the initial event. Conclusions Large, invasive pheochromocytoma can be safely and effectively managed with open resection in experienced hands, provided all efforts are made to achieve hemodynamic stabilization and to minimize. Catecholamine release before and during surgery.

Recent advances in the management of malignant pheochromocytoma and paraganglioma: focus on tyrosine kinase and hypoxia-inducible factor inhibitors

Inactivating mutations of the succinate dehydrogenase subunit B (SDHB) gene and the subsequent stabilization and activation of the hypoxia-inducible factor 2-alpha (HIF2α) unit are recognized hallmarks associated with the development of metastatic pheochromocytomas and paragangliomas (MPPG). Despite this discovery, the development of systemic therapies for patients with MPPG has been very slow. The rarity of the disease, the lack of preclinical animal models, and the impracticable development of large clinical trials has hindered the therapeutic progress for MPPG. Chemotherapy and low-specific activity 131meta-iodo-benzyl-guanidine (MIBG) (manufactured by simple isotope exchange methodology) led to positive clinical responses in about a third of patients. Molecular targeted therapies were introduced into oncological clinical practice at the beginning of the 21st century. These therapies have been demonstrated to be effective for patients with cancers that previously exhibited limited responses to systemic chemotherapy, such as kidney and thyroid carcinomas and pancreatic neuroendocrine tumors. The pathogenesis of MPPG overlaps in some way with the pathogenesis of kidney, medullary thyroid, and pancreatic neuroendocrine carcinomas, providing scientific support to explore molecular targeted therapies such as tyrosine kinase and HIF inhibitors.

Other nuclear cardiological investigations

This chapter explains the imaging protocol physiological properties and clinical value of other nuclear cardiological investigations. It covers iodine-123-labelled radiopharmaceuticals, iodine-123-meta-iodo-benzyl-guanidine (123I-MIBG), β‎-methyl-p-[123I]iodo-phenyl-pentadecanoic acid (123I-BMIPP), and Tc-phosphate scintigraphy for cardiac amyloidosis, exploring both practical and clinical aspects. Specific prognoses and diagnoses are also detailed for the relevant investigation, including systolic heart failure, coronary artery disease, and cardiac amyloidosis.

Microwave Irradiation Assisted Synthesis 4-Hydroxy 3-Iodobenzylguanidine(HIBG)

Meta-iodo benzyl guanidine(MIBG) is an analogue of Noradernalin transmitter. When radiolabelled with 123 I and 131I , used for scan and diagnosis Adernal’s tumor. Labeled MIBG with 131I used in therapy of Neuroblastoma , Pheochromocytoma , Carcinoidsyndome and Neuroendocrine tumors. In our continuing efforts to develop MIBG analogues with higher therapeutic efficacy, we recently evaluated the structure-activity characteristics of several analogues of MIBG. We are interested in developing HIBG analogues containing hydroxyl at the 4-postion oF HIBG.generous of the some groups to activate the aromatic ring of a drug towards electrophilic radiodiodination may have merit .The resistance of HIBG to in vivo radiodiodination and amenability to kit production make it a strong candidate for clinical evaluation as a pheochromocytoma and neuroblastoma localzing agent. Microwave assisted heating under controlled conditions has been shown to be an invaluable technology for organic chemistry and during discovery applications since it often rise yield and dramatically reduce reaction times, typically form days or hours to minutes or even seconds.Microwave Irradiation Assisted Synthesis of HIBG is started to produce 4-methoxybenzylamine. 4-methoxybenzylamine and hydriodic acid are mixed and heated for this purpose. Then under MBR condition 4-Hydroxybenzyl guanidine in sulphate form is prepared with additional Cyanamide and Sulphuric acid. After that Iodination is preformed under MBR condition and 4-Hydroxy-3-iodobenzyl guanidine sulphate formed , that can labeled with 131I and exchange to labeled 4-Hydroxy-3-iodobenzyl guanidine sulphate.