I-123 Metaiodobenzylguanidine Research Articles

Trends in analgesia-sedation of pediatric patients receiving I-131 MIBG in the pediatric intensive care unit: A report from the Pediatric Health Information System database.

Children with neuroblastoma receiving I-131 metaiodobenzylguanidine (MIBG) therapy require sedation-analgesia for strict radiation safety precautions during MIBG infusion and clearance. We evaluated the sedation-analgesia trends of patients undergoing MIBG therapy using the Pediatric Health Information System (PHIS) database. Retrospective data from 476 patient encounters from the PHIS from 2010 to 2019. Total 240/476 (50.45%) children evaluated were under 6years of age. Compared to 2010, in 2018 there was a decrease in benzodiazepine infusion use (60% vs. 40%, p<.04), as well as a decrease in use of opiate infusion (35% vs. 25%, p<.001). Compared to 2010, in 2018 we report an increase in the use of ketamine (from 5% to 10%, p<.002), as well as an increase in dexmedetomidine use (0% vs. 30%, p<.001). Dexmedetomidine was the most used medication in the 0-3years age group compared to children older than 3years of age (14.19% vs. 5.80%, p<.001). Opiate was the most used medication in children greater than 3years compared to the 0-3-year age group (36.23 vs. 23.87, p<.05). Using PHIS data, we discovered considerable variability in the medications used for sedation in patients undergoing MIBG therapy. Although benzodiazepines and opioids were the most used agents, there was a trend toward decreasing use of benzodiazepines and opioids in these patients. Furthermore, there has been an increasing trend in the use of dexmedetomidine and ketamine.

Safety and efficacy of multiple-dose versus single-dose MIBG therapy in patients with refractory pheochromocytoma and paraganglioma: a single-center retrospective analysis.

To investigate the incidence of adverse events (AEs) following single and multiple administrations of I-131 metaiodobenzylguanidine (MIBG) therapy for inoperable pheochromocytomas and paragangliomas (PPGLs). A single-center retrospective study was conducted on patients with inoperable PPGLs who underwent I-131 MIBG therapy between January 2000 and December 2020. A total of 28 patients with available electronic medical records were included. The treatment consisted of a single intravenous administration of 150mCi (5.55GBq) of I-131 MIBG. We evaluated the first MIBG treatment and repeated MIBG treatments performed within 200days of the previous treatment. AEs for each treatment were evaluated using CTCAE version 4.0, and the statistical analysis was conducted at a significance level of p < 0.05. Objective response based on RECIST 1.1 criteria and biochemical response based on urinary catecholamines were assessed. The study included a total of 63 administrations, consisting of 28 single administrations (SAs), including the first administration for all 28 cases, and 35 multiple administrations (MAs), which included the second or later administrations. Hematological AEs were evaluable for 23 SAs and 29 MAs. Grade 3 or higher leukopenia occurred in 9.8% of all administrations, and Grade 3 or higher lymphopenia in 23.5%; both were manageable through observation. There were no significant differences in clinical AE Grades 1-2 (p = 0.32), hematological AE Grades 1-2 (p = 0.22), or hematological AE Grades 3-4 (p = 0.12) between MAs and SAs. Statistical analysis for each type of AE revealed significant increases in leukopenia (p < 0.01) and lymphopenia (p = 0.04). No significant difference in anemia, thrombocytopenia, or neutropenia was observed between MAs and SAs. There was no significant increase in the incidence rate of Grade 3 or higher hematological AEs for any of the parameters. The objective response rate was 0% for SAs and 36% for MAs. Biochemical response rates were 18% for SAs and 67% for MAs. In I-131 MIBG therapy for PPGLs, multiple administrations significantly increased only Grade 1 or 2 lymphopenia and leukopenia compared to single administration.

Pediatric neuroblastoma with intraspinal extension: the role of surgical management.

Neuroblastoma with spinal involvement accounts for up to 30% of pediatric spinal tumors and can cause profound neurological deficits. Chemotherapy is the preferred treatment option, but in select patients resection may be indicated. The goal of this study was to identify preoperative factors that led to early surgical intervention, with a specific emphasis on identifying differences on long-term neurological function and spinal deformity in the recent treatment era. A retrospective chart review was performed on all children diagnosed with neuroblastoma at a single institution from 2007 to 2020. Patient demographics, symptoms (motor deficit and sphincter dysfunction), and tumor characteristics (e.g., 123I metaiodobenzylguanidine [MIBG] avidity, MYCN amplification, chromosomal abnormality, pathology, catecholamine secretion, and stage) were recorded. Spine involvement included neural or vertebral extension, spinal cord compression, and/or T2 signal change on MRI. Survival, neurological status (motor deficit, sphincter dysfunction), and spine deformity at last follow-up were compared using univariate and multivariate analyses. The variables that contributed to neurological and deformity outcome were assessed with binomial logistic and linear regression models using R software. Seventy-seven of the 160 patients with neuroblastoma had spinal neuroblastoma, meaning either bone metastases alone (n = 43) or intraspinal extension with or without neurological deficit (n= 34). Most patients with spinal neuroblastoma were treated with chemotherapy and/or radiation therapy (97% and 57%, respectively). Resection of the spinal tumor was performed in 14 (18%) patients, all of whom also received chemotherapy. Between the surgical and nonsurgical patients, no baseline demographic differences were found. However, surgical patients were more likely to present with either motor deficits (50% vs 5%, p = 0.0011) or bladder/bowel dysfunction (14% vs 0%, p 0.035), and a shorter median time to onset of neurological symptoms (33 vs 80 days, p = 0.0096). Surgical patients also had a significantly shorter median overall survival (33.0 vs 54 months, p = 0.014). Of the 14 patients who underwent spine surgery, 2 patients underwent surgery at the time of diagnosis while the remaining 12 underwent initial chemotherapy followed later by resection. The 2 patients who underwent initial surgery had excellent outcomes, with neither long-term motor or bowel/bladder deficits nor spinal deformity. Surgical patients had shorter overall survival. However, the 2 patients with radiographic evidence of cord compression and acute neurological symptom onset who underwent initial, immediate surgery within 3 days of diagnosis had fewer long-term neurological deficits than surgical patients who underwent initial trials of chemotherapy. Thus, acute decompression may provide benefit in carefully selected patients with acute neurological deficits and cord compression on imaging.

FRI265 I123-MIBG Positive, CU64-Dotatate PET Negative Pheochromocytoma In A Patient With Bilateral Adrenal Incidentalomas

Abstract Disclosure: P. Pagadala: None. V. Patel: None. Bilateral incidental adrenal nodules represent 10-23% of all incidental adrenal nodules. Most are benign nonfunctioning adenomas however these can be catecholamine-secreting tumors that arise from chromaffin cells of the adrenal medulla called pheochromocytomas. Identifying pheochromocytoma using anatomic imaging alone in cases of bilateral adrenal nodules is challenging. Functional imaging with radioisotope tracers can be helpful such as MIBG (meta-iodobenzylguanidine) and DOTATATE scans. We describe a case of pheochromocytoma, which was negative on DOTATATE but positive on MIBG scan which localized the pheochromocytoma. A 65-year-old male with a history of hypertension, chronic kidney disease and obstructive sleep apnea was found to have bilateral adrenal nodules on routine imaging. MRI abdomen showed a right adrenal nodule 1.7cm x 1.8cm x 1.7cm and a left adrenal nodule 2.3 cm in maximum dimension. He had no apparent symptoms of catecholamine excess. Biochemical testing revealed elevated total plasma metanephrines on serial assessments along with elevated 24-hour urine dopamine levels. A CT scan with adrenal protocol further characterized the right adrenal nodule with precontrast density of 43 Hounsfield Units (HU) with a rapid washout of 75% within 5 minutes, consistent with benign adrenal adenoma. The left adrenal gland had 2 nodules. A smaller superior nodule 1.3 cm AP x 1.0 cm transverse x 0.9 cm craniocaudal in size, density of -3 HU on the precontrast images, with approximately 85% washout most consistent with a benign adrenal adenoma. A larger inferior nodule was 2.3 cm AP x 2.2 cm transverse x 2.3 cm craniocaudal in size and precontrast density of 32 HU, rising to 58 HU during the portal venous phase and remaining at about 58 HU on the delayed images, indicating no significant washout and is indeterminate. A Cu64 labeled DOTATATE scan showed the 1.6 cm right adrenal nodule demonstrated activity similar to that of contralateral background adrenal activity. There was no comment regarding the two left adrenal nodules. A I123 MIBG scan showed the larger of the two left adrenal nodules had a strong uptake of the MIBG highly likely to be a pheochromocytoma. The smaller left adrenal nodule and the right adrenal nodule had no significant MIBG uptake, making these adrenal adenomas. The patient underwent left robotic adrenalectomy and pathology confirmed a 2.3 cm pheochromocytoma in addition to adrenocortical nodular disease. Three months post-surgery, plasma and 24-hour urinary measurements for metanephrines and catecholamines had normalized. Further research is needed to assess the benefit of I123MIBG when DOTATATE is negative. A potential cause of false negatives on DOTATATE is variability in somatostatin receptor subtype expression. Better imaging modalities for pheochromocytomas and guidelines for the management of bilateral adrenal nodules would assist in treatment decisions. Presentation: Friday, June 16, 2023

Machine learning-based prediction of conversion coefficients for I-123 metaiodobenzylguanidine heart-to-mediastinum ratio

PurposeWe developed a method of standardizing the heart-to-mediastinal ratio in 123I-labeled meta-iodobenzylguanidine (MIBG) images using a conversion coefficient derived from a dedicated phantom. This study aimed to create a machine-learning (ML) model to estimate conversion coefficients without using a phantom. Methods210 Monte Carlo (MC) simulations of 123I-MIBG images to obtain conversion coefficients using collimators that differed in terms of hole diameter, septal thickness, and length. Simulated conversion coefficients and collimator parameters were prepared as training datasets, then a gradient-boosting ML was trained to estimate conversion coefficients from collimator parameters. Conversion coefficients derived by ML were compared with those that were MC simulated and experimentally derived from 613 phantom images. ResultsConversion coefficients were superior when estimated by ML compared with the classical multiple linear regression model (root mean square deviations: 0.021 and 0.059, respectively). The experimental, MC simulated, and ML-estimated conversion coefficients agreed, being, respectively, 0.54, 0.55, and 0.55 for the low-; 0.74, 0.70, and 0.72 for the low-middle; and 0.88, 0.88, and 0.88 for the medium-energy collimators. ConclusionsThe ML model estimated conversion coefficients without the need for phantom experiments. This means that conversion coefficients were comparable when estimated based on collimator parameters and on experiments.

Biomarker response to high-specific-activity I-131 meta-iodobenzylguanidine in pheochromocytoma/paraganglioma.

The objective of this study is to present the complete biomarker response dataset from a pivotal trial evaluating the efficacy and safety of high-specific-activity I-131 meta-iodobenzylguanidine in patients with advanced pheochromocytoma or paraganglioma. Biomarker status was assessed and post-treatment responses were analyzed for catecholamines, metanephrines, and serum chromogranin A. Complete biomarker response (normalization) or partial response, defined as at least 50% reduction from baseline if above the normal range, was evaluated at specified time points over a 12-month period. These results were correlated with two other study objectives: blood pressure control and objective tumor response as per RECIST 1.0. In this open-label, single-arm study, 68 patients received at least one therapeutic dose (~18.5 GBq (~500 mCi)) of high-specific-activity I-131 meta-iodobenzylguanidine. Of the patients, 79% and 72% had tumors associated with elevated total plasma free metanephrines and serum chromogranin A levels, respectively. Best overall biomarker responses (complete or partial response) for total plasma free metanephrines and chromogranin A were observed in 69% (37/54) and 80% (39/49) of patients, respectively. The best response for individual biomarkers was observed 6-12 months following the first administration of high-specific-activity I-131 meta-iodobenzylguanidine. Biochemical tumor marker response was significantly associated with both reduction in antihypertensive medication use (correlation coefficient 0.35; P = 0.006) as well as objective tumor response (correlation coefficient 0.36; P = 0.007). Treatment with high-specific-activity I-131 meta-iodobenzylguanidine resulted in long-lasting biomarker responses in patients with advanced pheochromocytoma or paraganglioma that correlated with blood pressure control and objective response rate. ClinicalTrials.gov number: NCT00874614.

Carotid Artery Revascularization Improves Cardiac Sympathetic Nerve Activity in Patients With Carotid Artery Stenosis.

The carotid sinus baroreceptor reflex controls the neural regulation of blood pressure. Baroreceptor disorders due to carotid sinus atherosclerosis have detrimental cardiovascular effects. This study investigated the medium-term effects of carotid artery revascularization (CAR) on sympathetic and cardiac function and systemic blood pressure variability in patients with carotid artery stenosis. This study included 21 consecutive patients (median age 70 years, 18 men) with carotid artery stenosis scheduled for CAR. 123I metaiodobenzylguanidine (MIBG) scintigraphy, echocardiography, brain natriuretic peptide levels, 24-h Holter electrocardiography (ECG), and ambulatory blood pressure monitoring assessed approximately 3 months postoperatively were compared to preoperative data. All 21 enrolled patients underwent CAR. Carotid artery stenting was done in three patients with cardiovascular risk or anatomical difficult for carotid endarterectomy. The mean common carotid artery end-diastolic velocity improved significantly (P < 0.01) by 1.6-fold, from 10.8 ± 3.2 to 16.1 ± 7.1 cm/s. In 123I-MIBG scintigraphy, the heart-to-mediastinum (H/M) count ratio was significantly higher than preoperatively (from 2.66 ± 0.48 to 2.86 ± 0.56, P = 0.03). Holter ECG analysis revealed a significant decrease in the low-frequency/high-frequency (LF/HF) ratio compared to preoperatively (from 2.17 ± 1.20 to 1.62 ± 0.68, P = 0.04). These findings suggest decreased myocardial sympathetic activation. In echocardiography, the tissue Doppler-derived e' increased, and E/e' decreased significantly (P < 0.05) from 11.7 ± 5.1 to 10.1 ± 4.0, suggesting an improved left ventricular diastolic capacity. The mean 24-h and nighttime blood pressures were unchanged. CAR in patients with carotid stenosis may provide medium-term improvement in cardiac sympathetic nerve activity and left ventricular diastolic dysfunction.

I-131 metaiodobenzylguanidine therapy is a significant treatment option for pheochromocytoma and paraganglioma.

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumours of chromaffin cells. Several modalities are currently available to treat patients with PPGL. These treatment modalities include surgery, chemotherapy, molecular targeted therapy and radiopharmaceuticals. I-131 metaiodobenzylguanidine (mIBG), a classic radiopharmaceutical, can be taken up through specific receptors and sited into many, but not all, PPGL cells. Many studies have investigated the efficacy and toxicity of I-131 mIBG therapy. These studies reported significant results in terms of objective, hormonal and symptomatic responses as well as tolerable toxicities in patients. This article reviews the reported experiences of patients who underwent I-131 mIBG therapy for PPGL with a focus on functions and deficiencies of the therapy.

Relationship between heart rate response and cardiac innervation in patients with suspected or known coronary artery disease

BackgroundChronotropic response to pharmacological stress test is blunted in patients with autonomic neuropathy. The relationship between heart rate (HR) changes during pharmacological stress test and cardiac autonomic dysfunction has not been fully investigated. We assessed the potential interplay between HR response (HRR) and myocardial innervation in patients with suspected or known coronary artery disease (CAD). Methods and ResultsWe studied 71 patients with suspected or known CAD referred to pharmacological stress myocardial perfusion imaging and 123I metaiodobenzylguanidine (123I-MIBG) cardiac scintigraphy. HRR was calculated as the maximum percent change from baseline according to the formula: (peak HR − rest HR)/rest HR × 100. 123I-MIBG heart-to-mediastinum (H/M) ratio was calculated and a late H/M ratio < 1.6 was considered abnormal. HRR progressively decreased with decreasing late H/M ratio (P for trend = 0.02) and a significant correlation between HRR and late H/M ratio (P = 0.03) was observed. The addition of HRR to a model including age, diabetes, known CAD, left ventricular ejection fraction, and stress-induced ischemia added incremental value in predicting an abnormal late H/M ratio, increasing the global chi-square from 8.09 to 13.8 (P = 0.02). ConclusionsThe relationship between HRR and cardiac sympathetic innervation in patients with suspected or known CAD confirms a strong interplay between cardiac response to stress tests and cardiac autonomic activation. This finding suggests that HRR may be used as a surrogate for assessing cardiac sympathetic function.

Usefulness of semi-quantitative analysis in 123I metaiodobenzylguanidine SPECT/CT for the differentiation of pheochromocytoma and cortical adenoma.

123I metaiodobenzylguanidine (MIBG) scintigraphy is a useful tool for the diagnosis of pheochromocytomas (PHEOs), but some PHEOs are difficult to differentiate from cortical adenoma (CA) or normal adrenal uptake by visual evaluation alone. A new semi-quantitative analysis using 123I MIBG SPECT/CT is thus expected. Herein, we introduce the tumor-to-liver count ratio (T/L) and the tumor-to-muscle count ratio (T/M). We examined the cases of 21 patients with PHEOs (10 males, 11 females; age 24-80, median 61 years) and 23 patients with CA (15 males and 8 females, age 30-78, median 58 years). The visual scoring based on 123I MIBG planar images (planar score) and SPECT images (SPECT score) was used as the conventional evaluation. Using 123I MIBG SPECT/CT findings, we calculated the semi-quantitative values of the count ratio using the maximum or mean count of the tumor and the liver or muscle as the reference organ (T/Lmax, T/Lmean, T/Mmax and T/Mmean). Each evaluation of the PHEOs and CAs was compared, and the diagnosing performance was evaluated based on an ROC analysis. The area under curve (AUC) values were as follows: the planar score, 0.833; SPECT score, 0.813; T/Lmax, 0.986; T/Lmean, 0.975; T/Mmax, 0.955; and T/Mmean, 0.933. The AUC for T/Mmax was significantly higher than those of the planar score, and SPECT score by ROC analysis (p < 0.01 each). The semi-quantitative value of 123I MIBG SPECT/CT is more useful than the conventional visual evaluation for differentiating PHEOs from CAs.

Transplantation for ultra high-risk neuroblastoma patients: effect of tandem autologous stem cell transplantation

Aim: Neuroblastoma is a tumor with a high mortality rate originating from primitive sympathetic ganglion cells. In recent years, the definition of "ultra high-risk" has been used, in which the response to treatment is added in addition to the disease characteristics. In this study, the results of tandem high-dose Iodine 131 (131I) metaiodobenzylguanidine (MIBG) and tandem autologous hematopoietic stem cell transplantation (HSCT) in patients who were diagnosed as refractory after first-line treatments and considered with ultra-high risk nöroblastom (NBL) in Erciyes University Medical Faculty Pediatric Bone Marrow Transplant Center were shared.&#x0D; Material and Method: Eleven patients who underwent tandem MIBG and autologous HSCT with the diagnosis of refractory/ultra high-risk NBL between 2011 and 2021 were included in the study. Patient's data were obtained retrospectively using an electronic or manuscript medical record.&#x0D; Results: Tandem autologous HSCT and MIBG treatment were applied to 11 patients with a median age of 40.5 months who were diagnosed with refractory/ultra high-risk neuroblastoma. In our study, the overall survival rate was 54.5% and event-free survival (EFS) was 39% at a median follow-up of 20.7 (7.8-105.6) months. Of the 6 surviving patients, 4 are followed in complete remission and 2 in partial remission.&#x0D; Conclusion: Our study is the only study that includes a group of patients who received tandem high-dose MIBG and tandem autologous HSCT transplantation in refractory NBL patients without cytokine and immunotherapy. Tandem transplantation and MIBG therapy in ultra-high-risk NBL cases remain promising with acceptable toxicity. Adding immunotherapy to this treatment protocol and combining it with new treatment modalities such as anaplastic lymphoma kinase (ALK), which also takes into account genetic characteristics, may increase survival and event-free survival rates.

Aceruloplasminemia: a multimodal imaging study in an Italian family with a novel mutation.

Structural abnormalities in thalami and basal ganglia, in particular the globus pallidus (GP), are a neuroimaging hallmark of hereditary aceruloplasminemia (HA), yet few functional imaging data exit in HA carriers. This study investigated the iron-related structural and functional abnormalities in an Italian HA family. Multimodal imaging was used including structural 3T MRI, functional imaging (SPECT imaging with 123I-ioflupane (DAT-SPECT), cardiac 123I metaiodobenzylguanidine (123I-MIBG) scintigraphy, and 18F-fluorodeoxyglucose (18F-FDG)-PET imaging). In the proband, MRI and scintigraphic evaluations were performed at baseline, 2 and 4years (structural imaging), and 2years of follow-up period (functional imaging). We investigated two cousins carrying a novel splicing homozygous mutation in intron 6 (IVS6 + 1 G > A) of CP gene. Interestingly, MRI features in both subjects were characterized by marked iron accumulation in the thalami and basal ganglia nuclei, while GP was not affected. MRI performed in the proband at 2 and 4years of follow-up confirmed progressive neurodegeneration of the thalami and basal ganglia without the involvement of GP. Functional imaging showed reduced putaminal DAT uptake in both cousins, whereas cardiac MIBG and FDG uptakes performed in the proband were normal. Longitudinal scintigraphic investigations did not show significant changes over the time. For HA carriers, our findings demonstrate that GP was spared by iron accumulation over the time. The nigrostriatal presynaptic dopaminergic system was damaged while the cardiac sympathetic system remained longitudinally preserved, thus expanding the imaging features of this rare inherited disorder.

突然の心不全を契機に発見された基礎疾患のない若年者の褐色細胞腫の1例(A case of pheochromocytoma in young patient without cardiovascular risk factors that found out due to sudden heart failure)

要旨 30代女性。呼吸苦で救急受診し，胸部X線で全肺野スリガラス陰影，computed tomographyで肺水腫・右副腎腫瘍を認めた。経胸壁心エコーで推定左室駆出率 約30%・全周性壁運動低下を認め，急性心不全として緊急入院した。人工呼吸管理後，呼吸苦や頻呼吸は消失し，酸素化も速やかに改善した。第2病日，胸部X線・経胸壁心エコー所見も正常となり抜管した。入院時病態は不明のまま，第9病日退院した。入院時，偶発的に発見された右副腎腫瘍から褐色細胞腫による肺水腫・心機能低下を考慮し，退院後に精査された。血中カテコラミン濃度・123I–MIBG（metaiodobenzylguanidine）シンチグラフィ・クロニジン負荷試験などより褐色細胞腫と診断された。その後，右副腎摘出術により寛解した。入院時の症状は褐色細胞腫から多量に分泌されたカテコラミンによる心不全であったと考えられた。

Creation of mortality risk calculator using a I-123 mIBG-based machine learning model: differential prediction of arrhythmic death and heart-failure death

Abstract Funding Acknowledgements Type of funding sources: None. Background Although I-123 meta-iodobenzylguanidine (mIBG) has been applied to patients with chronic heart failure (CHF), a diagnostic tool for differential prediction of fatal arrhythmic events (ArE) and heart-failure death (HFD) has been pursued. Purpose The aim of this study was to create a calculator of mortality risk for differentiating mode of cardiac death using a machine learning (ML) method, and to test the accuracy in a new cohort of patients with CHF. Methods A total of 529 patients with CHF was used as the training database for ML. The ArE group consisted of patients with arrhythmic death, sudden cardiac death and appropriate therapy by implantable cardioverter defibrillator. A heart-to-mediastinum ratio (H/M) standardized to the medium-energy collimator condition was calculated with a planar anterior mIBG scintigram. The best classifier models for predicting HFD and ArE were determined by four-fold cross validation. Input variables included age, sex, New York Heart Association (NYHA) functional class, left ventricular ejection fraction, ischemic etiology, mIBG H/M and washout rate, and b-type natriuretic peptide (BNP) or NT Pro BNP, estimated glomerular filtration rate, hemoglobin, and complications such as diabetes and hypertension. After creating the ML-based model, the constructed classifier functions for ArE, HFD, and survival were exported for subsequent use. A new cohort of patients (n = 312, age 67 ± 13 years, 2015 or later) was used to test the ML-based model. Results The training database included 141 events (27%) with ArE (7%) and HFD (20%). Receiver-operating characteristic analysis by four-fold validation showed area under the curve value of 0.90 for HFD and 0.73 for ArE. Among various ML methods, the logistic regression method demonstrated the most stable calculation of the probability of ArE followed by random forest and gradient boosted tree methods. Therefore, the logistic-regression method was used for calculating both HFD and ArE probabilities. In the test cohort, patients with a high HFD probability &amp;gt;8% resulted in 6.3-fold higher HFD than those with low probability (≤ 8%). Patients with high ArE probability &amp;gt;8% showed 2.5-fold higher ArE than those with low probability (≤ 8%). Conclusion The ML-based mortality risk calculator could be used for stratifying patients at high and low risks, which might be useful for estimating appropriate treatment strategy.

123I metaiodobenzylguanidine (MIBG) uptake predicts early relapse of neuroblastoma using semi-quantitative SPECT/CT analysis

Objective123I metaiodobenzylguanidine (MIBG) scintigraphy is a useful tool for the diagnosis of neuroblastoma (NB). MIBG uptake is correlated with norepinephrine transporter expression; hence, it is expected that high-MIBG tumors would be more highly differentiated and have a better prognosis than those with lower expression. We have introduced a method of assessing MIBG accumulation semi-quantitatively using SPECT/CT fusion images. The purpose of this study was to evaluate the relationship of 123I MIBG uptake measured by semi-quantitative values of SPECT/CT and early relapse of NB.MethodsWe studied the cases of 11 patients (5 males and 6 females, age 5–65 months, median age 20 months) with histopathologically proven NB between April 2010 and March 2015. The early-relapse group was defined as patients who had relapsed within 3 years after the first 123I MIBG SPECT/CT exam. Other patients were classified as the delay-relapse group. Uptake of MIBG was evaluated using the count ratio of tumor and muscles. T/Mmax and T/Mmean were defined as follows: T/Mmax = max count of tumor/max count of muscle, T/Mmean = mean count of tumor/mean count of muscle.ResultsThe average T/Mmean values of the early-relapse group and delay-relapse group were 2.65 ± 0.58 and 7.66 ± 2.68, respectively. The T/Mmean values of the early-relapse group were significantly lower than those of delay-relapse group (p < 0.05). The average T/Mmax of the early-relapse group and delay-relapse group were 8.86 ± 3.22 and 16.20 ± 1.97, respectively. There was no significant difference in T/Mmax values between the two groups.ConclusionsLow 123I MIBG uptake using semi-quantitative SPECT/CT analysis was correlated with early relapse of NB.

Low-Dose, Low-Specific Activity 131I-metaiodobenzyl Guanidine Therapy in Metastatic Pheochromocytoma/Sympathetic Paraganglioma: Single-Center Experience from Western India.

Introduction:Radionuclide therapy is a promising treatment modality in metastatic pheochromocytoma/paraganglioma (PPGL). There is scarce data on 131I-metaiodobenzyl guanidine (131I-MIBG) therapy from the Indian subcontinent. Hence, we aim to study the safety and effectiveness of low-dose, low-specific activity (LSA) 131I-MIBG therapy in patients with symptomatic, metastatic PPGL.Methods:Clinical, hormonal, and radiological response parameters and side effects of LSA 131I-MIBG therapy in patients with symptomatic, metastatic PPGL were retrospectively reviewed. World health organizations’ (WHO) symptomatic, hormonal, and tumor response, and response evaluation criteria in solid tumors (RECIST1.1) criteria were used to assess the response.Results:Seventeen (PCC: 11, sympathetic PGL: 06) patients (15 with disease progression) received low-dose LSA 131I-MIBG therapy. Complete remission (CR), partial remission (PR), stable disease (SD), and progressive disease (PD) were 18% (3/17), 24% (4/17), 18% (3/17), and 41% (7/17), respectively, for WHO symptomatic response; 20% (2/10), 10% (1/10), 30% (3/10), and 40% (4/10), respectively, for WHO hormonal response; and 19% (3/16), 6% (1/16), 31% (5/16), and 44% (7/16), respectively for tumor response based on RECIST1.1. All patients with symptomatic PD and 50% (2/4) with hormonal PD had progression as per RECIST1.1 criteria. Side effects included thrombocytopenia, acute myeloid leukemia, mucoepidermoid carcinoma, and azoospermia in 6% (1/17) each.Conclusions:Our study reaffirms the modest efficacy and safety of low-dose, LSA 131I-MIBG therapy in patients with symptomatic, metastatic PPGL. Symptomatic, but not hormonal, progression after 131I-MIBG therapy correlates well with tumor progression and should be further evaluated with imaging. In resource-limited settings, anatomic imaging alone may be used to assess tumor response to 131I-MIBG therapy.

Prognostic significance of cardiac 123I-MIBG SPECT imaging in patients with acute decompensated heart failure with preserved left ventricular ejection fraction

Abstract Background Cardiac sympathetic nerve dysfunction, which is assessed by I-123 metaiodobenzylguanidine (MIBG) imaging, is associated with the poor outcomes in patients with heart failure (HF). Most of the literature on the use of 123I-MIBG imaging is based on planar images in patients with chronic HF and reduced left ventricular ejection fraction (HFrEF), because It is technically challenging to conduct precise 123I-MIBG SPECT analysis in globally denervated heart, which is frequently observed in HFrEF patients. There was no information available on cardiac sympathetic nerve dysfunction evaluated by cardiac MIBG SPECT imaging in acute decompensated HF (ADHF) patients with preserved left ventricular ejection fraction (HFpEF). Purpose We aimed to clarify the prognostic significance of 123I-MIBG SPECT myocardial imaging in ADHF patients with HFpEF. Methods We enrolled 183 patients who were admitted for ADHF with HFpEF, discharged with survival. All patients underwent cardiac MIBG imaging at the timing of discharge. The cardiac MIBG heart to mediastinum ratio (H/M) was calculated on the early image and the delayed image (late H/M). We studied 156 patients after excluding 27 patients whose MIBG SPECT reconstruction was difficult due to too low MIBG uptake or extracardiac accumulation interference. SPECT analysis on the delayed image was conducted by using CardioBull, a fully automated software for the quantification of I-123 MIBG SPECT. All of 17 regional tracer uptake were compared with normal control database. A scoring algorithm for the evaluation of low uptake employs a 5-point scoring system as 0–4 for normal, mildly abnormal, moderately abnormal, severe abnormal, and perfusion defect, respectively. The summed severity (SSS) scores were obtained by summing the score for all segments. SSS could range from 0 to 68. The endpoint of this study is cardiac events defined as the composite of unplanned heart failure hospitalization and cardiac death. Results During a mean follow up period of 2.4±1.6 years, 60 patients reached cardiac events. SSS was significantly high in patients with than without cardiac events (20 [10–27] vs 7 [4–16], p&amp;lt;0.0001). SSS (p&amp;lt;0.0001) was significantly associated with cardiac events after multivariable Cox adjustment of age, sex, creatinine and log-transformed BNP level, although late H/M showed the significant association with the endpoint at the univariate Cox analysis. Kaplan-Meier analysis showed that patients with high SSS (&amp;gt;10, defined by median) had significantly greater risk of cardiac event (56% vs 21%, Hazard ratio: 3.56 (2.00–6.33, p&amp;lt;0.0001). ROC curve analysis showed that area under the curve (AUC) of SSS was 0.746 [95% CI:0.670, 0.812], which was significantly higher than that of late H/M (0.618 [95% CI:0.537, 0.695]) (p=0.0159). Conclusion Cardiac MIBG SPECT imaging was useful for risk stratification in ADHF patients with HFpEF. Funding Acknowledgement Type of funding source: None

Long-term serial changes of cardiac sympathetic nerve dysfunction in acute decompensated heart failure patients with reduced, mid-range and preserved left ventricular ejection fraction

Abstract Background Cardiac sympathetic nerve dysfunction, which is assessed by I-123 metaiodobenzylguanidine (MIBG) imaging, is associated with the poor outcomes in patients with chronic heart failure (CHF). Serial evaluation of cardiac MIBG imaging was shown to be useful for predicting adverse outcome in CHF. However, there was no information available on long-term serial changes of cardiac sympathetic nerve dysfunction after discharge of acute decompensated heart failure (ADHF) hospitalization. Purpose We aimed to clarify the serial change of cardiac MIBG imaging parameter in long-term after discharge of heart failure hospitalization, especially relating to HFrEF (LVEF&amp;lt;40%), HFmrEF (40%≤LVEF&amp;lt;50%) and HFpEF (LVEF≥50%). Methods We studied 112 patients (HFrEF; n=44, HFmrEF; n=23 and HFpEF; n=45) who were admitted for ADHF, discharged with survival and without heart failure hospitalization during follow-up period. All patients underwent cardiac MIBG imaging at the timing of discharge, in 6–12 months and in 18–24 months after discharge. The cardiac MIBG heart to mediastinum ratio (H/M) was calculated on the early image and the delayed image (late H/M). The cardiac MIBG washout rate (WR) was calculated from the early and delayed planar images after taking radioactive decay of I-123 into consideration. Results In HFrEF patients, late H/M was significantly improved from discharge to 6–12 months data (1.60±0.24 vs 1.75±0.31, p&amp;lt;0.0001). Late H/M of HFmrEF patients was also significantly improved from discharge to 18–24 months data (1.71±0.27 vs 1.84±0.29 p=0.043). On the other hand, late H/M of HFpEF patients was not significantly changed. As for WR, WR in HFrEF and HFmrEF patients was significantly improved from discharge to 18–24 months data, although WR of HFpEF was not significantly changed. Conclusion The improvement in cardiac sympathetic nerve dysfunction was observed in patients with HFrEF and HFmrEF, not in HFpEF, after the discharge of acute heart failure hospitalization. Funding Acknowledgement Type of funding source: None

Mucosa-associated lymphoid tissue (MALT) lymphoma developing in ectopic mediastinal thyroid tissue: a case report

BackgroundNormally located in the neck, ectopic mediastinal thyroid tissue consists of very rare ectopic thyroid tissue that does not connect to the thyroid gland. A patient with mucosa-associated lymphoid tissue (MALT) lymphoma that has developed in mediastinal thyroid tissue, to our best knowledge, has not been previously reported.Case presentationA 67-year-old woman presented with a superior mediastinal mass that was revealed by chest computed tomography (CT), an optional examination she hoped, during a medical checkup. Contrast-enhanced CT scan performed in our hospital for close examination confirmed the presence of a 2 × 1.3 cm poorly enhanced mass anterior to the trachea during the arterial phase. Magnetic resonance imaging depicted low signal intensity on T1-weighted images and high signal intensity on T2-weighted images. I-131 meta-iodobenzylguanidine did not accumulate in the mass. Serum levels of interleukin-2 receptor, catecholamine, and anti-acetylcholine receptor antibody were within the normal range. The mass was resected through a transverse neck incision for the diagnosis and treatment. The histopathological diagnosis of the specimen was ectopic mediastinal thyroid tissue associated with MALT lymphoma and chronic thyroiditis. Immunoglobulin heavy chain class switch recombination was identified. Fine-needle aspiration biopsy of the cervical thyroid showed chronic thyroiditis but not lymphoma. The patient’s postoperative thyroid function was normal. To date, the patient’s recovery has been uneventful, and she is being monitored without further treatment.ConclusionWe treated the patient with MALT lymphoma that developed in ectopic mediastinal thyroid tissue. This novel case illustrates a new differential diagnosis associated with ectopic mediastinal thyroid tissue.

Clinical significance of vanillylmandelic acid in neuroblastoma

Background: The second most common solid tumor in children is Neuroblastoma (NB). In about 90% of cases of NB, elevated levels of catecholamines or its metabolites are found in the urine or blood which includes Vanillylmandelic Acid (VMA) and Homovanillic Acid (HVA). Ferritin, Neuron-Specific Enolase (NSE) and Lactate Dehydrogenase (LDH) are commonly assessed in children suspected to have NB, and the levels of these markers are commonly used for differential diagnosis. Multiple clinical and imaging tests are needed for accurate patient assessment. Iodine 123(123I) Metaiodobenzylguanidine (MIBG) is the first-line functional imaging agent used in neuroblastoma imaging. To evaluate the utility of these marker present study was undertaken with 91 NB patients and 40 normal healthy control.Methods: The study comprised of blood samples and 24 hour’s urine sample from 40 normal healthy subjects and 91 untreated patients with histologically proven Stage III and IV NB cases referred to our institute. Method used for NSE was Enzyme Immunoassay (Elisa), serum Ferritin was MIA, LDH-photometry and VMA by Column Chromatography.Results: Amongst the parameters studied VMA showed highest sensitivity (91%), specificity (94.4%) positive predictive value (97.8%) and 85% negative predictive value at the cut off levels of 7mg/ ml of creatinine as compared to other studied parameters.Conclusions: This study suggests that the detection of VMA in combination with routine histological examination, MIBG scan, serum NSE and LDH may improve the diagnosis of Neuroblastoma.