Anatomic patterns of relapse and progression following treatment with 131 I-MIBG in relapsed or refractory neuroblastoma.

OBJECTIVES: Patients with metaiodobenzylguanidine (MIBG)-avid relapsed or refractory neuroblastoma after initial therapy may exhibit transient responses to salvage treatment with iodine-131 metaiodobenzylguanidine (131 I-MIBG). It is unclear whether disease progression following 131 I-MIBG treatment occurs in previously involved versus new anatomic sites of disease. Understanding this pattern of relapse will inform the use of consolidation therapy following 131 I-MIBG administration. METHODS: Patients with relapsed or refractory metastatic MIBG-avid neuroblastoma or ganglioneuroblastoma, who received single-agent 131 I-MIBG, had stable or responding disease 6-8 weeks following 131 I-MIBG, but subsequently experienced disease progression were included. MIBG scans were reviewed to establish anatomic and temporal evolution of MIBG-avid disease. RESULTS: A total of 84 MIBG-avid metastatic sites were identified immediately prior to MIBG therapy in a cohort of 12 patients. At first progression, a total of 101 MIBG-avid sites were identified, of which 69 (68%) overlapped with pre-treatment disease sites, while 32 (32%) represented anatomically new disease areas. Eight of 12 patients had one or more new MIBG-avid sites at first progression. Of the 69 involved sites at progression that overlapped with pre-treatment disease, 11 represented relapsed sites that had cleared following MIBG therapy, two were persistent but increasingly MIBG-avid, and 56 were stably persistent. CONCLUSIONS: Previously involved anatomic disease sites predominate at disease progression following 131 I-MIBG treatment. Nevertheless, the majority of patients progressed in at least one new anatomic disease site. This suggests that consolidation focal therapies targeting residual disease sites may be of limited benefit in preventing systemic disease progression following 131 I-MIBG treatment of relapsed or refractory neuroblastoma.

Estratificação de Risco e Avaliação da Atividade Simpática Cardíaca Utilizando Imagem Miocárdica com [123I] MIBG na Denervação Renal / Risk Stratification and Cardiac Sympathetic Activity Assessment Using Myocardial [123I] MIBG Imaging in Renal Denervation

Resumo A hiperativação do sistema nervoso simpático desempenha um papel central na fisiopatologia da hipertensão. O objetivo deste estudo foi avaliar a atividade simpática cardíaca e investigar o papel da cintigrafia miocárdica com metaiodobenzilguanidina com 123I ([123I] MIBG) na estratificação de risco cardiovascular de pacientes com hipertensão resistente tratados com denervação renal (DR). Dezoito pacientes foram incluídos neste estudo prospectivo (média de idade de 56 ± 10 anos, 27,8% mulheres). Ecocardiograma transtorácico, análise geral do sangue e cintilografia miocárdica com [(123I) MIBG] foram realizados antes e seis meses após a DR. Um paciente era considerado respondedor (R) se uma diminuição ≥ 5 mmHg na pressão arterial sistólica (PAS) média ambulatorial fosse observada no seguimento de seis meses. 66,7% dos pacientes foram R (diminuição na PAS de 20,6 ± 14,5 mmHg, vs. menos 8 ± 11,6 mmHg em não-respondedores (NR), p = 0,001). A relação coração-mediastino (RCM) inicial foi significativamente menor na linha basal no grupo R (1,6 ± 0,1 vs. 1,72 ± 0,1, p <0,02), mas semelhante em seis meses. Considerando os dois momentos no tempo, o grupo R teve valores iniciais de RCM mais baixos do que o grupo NR (p <0,05). Tanto o RCM tardio quanto a taxa de washout foram idênticos e nenhuma correlação significativa entre a resposta à DR ou qualquer índice de imagem com MIBG foi encontrada. A denervação renal efetivamente reduziu a pressão arterial na maioria dos pacientes, mas a imagem com [123I] MIBG não foi útil na previsão da resposta. Entretanto, houve evidência de overdrive do sistema nervoso simpático e, tanto a RCM inicial quanto tardia estavam reduzidas em geral, provavelmente colocando essa população em um risco maior de eventos adversos.

Abstract Hyperactivation of the sympathetic nervous system plays a central role in the pathophysiology of hypertension. The aim of this study was to assess cardiac sympathetic activity and investigate the role of myocardial123I-labelled meta-iodo benzyl guanidine ([123I] MIBG) scintigraphy in cardiovascular risk stratification of patients with resistant hypertension treated with renal denervation (RDN). Eighteen patients were included in this prospective study (mean age 56 ± 10 years old, 27.8% females). Transthoracic echocardiogram, general blood analysis and myocardial ([123I] MIBG scintigraphy were performed before and six-months after RDN. A patient was considered a responder (R) if a drop ≥ 5mmHg on mean systolic ambulatory blood pressure (BP) monitoring was observed at the six-month follow-up. 66.7% of patients were R (drop in systolic BP of 20.6 ± 14.5mmHg, vs minus 8 ± 11.6mmHg in non-responders (NR), p=0.001). Early heart-mediastinum ratio (HMR) was significantly lower at baseline in the R group (1.6 ± 0.1 vs 1.72 ± 0.1, p<0.02) but similar at six months. Considering both instants in time, the R group had lower early HMR values than the NR group (p<0.05). Both the late HMR and the washout rate were identical and no significant correlation between response to RDN or any MIBG imaging index was found. Renal denervation effectively lowered blood pressure in the majority of patients but [123I] MIBG was not useful in predicting the response. However, there was evidence of sympathetic overdrive and, both early and late HMR were overall reduced, probably putting this population at a higher risk of adverse events.

Iodine allergy: Common misperceptions.

PURPOSE: The current evidence regarding iodine-containing compounds and iodine allergy cross-reactivity is reviewed. SUMMARY: Iodine is an essential human nutrient found in the thyroid gland. It is used in the synthesis of the thyroid hormones thyroxine and triiodothyroxine. Patients who report having adverse reactions to iodine-containing substances are often labelled as having an "iodine allergy," which can result in delays in care or patients being denied essential iodinated contrast media (ICM) or other iodine-containing drugs. A literature review was conducted to evaluate the evidence regarding iodine allergy and iodine-containing drugs. Of 435 articles considered potentially appropriate for full review (plus 12 additional articles included on the basis of references from the eligible articles), 113 could not be obtained. After exclusion of 353 articles that did not meet all inclusion criteria, the remaining 81 articles were included in the review. The results of the literature review indicated that iodine has not been shown to be the allergen responsible for allergic reactions to iodinated contrast media, amiodarone, povidone-iodine, and other iodine-containing compounds. CONCLUSION: There is a lack of evidence to support cross-reactivity between iodine-containing compounds in so called iodine-allergic individuals.

A feasibility study of 99Tc m-MIBI/ 123I-MIBG dual-isotope cardiac imaging using CZT SPECT / 中华核医学与分子影像杂志

Objective:To study the feasibility of cardiac 99Tc m-methoxyisobutylisonitrile (MIBI)/ 123I-metaiodobenzylguanidine (MIBG) dual-isotope imaging with cadmium-zinc-telluride (CZT) SPECT. Methods:Using a heart phantom, 99Tc m-MIBI single-isotope imaging and 99Tc m-MIBI/ 123I-MIBG dual-isotope imaging were acquired separately. Model A, B, C represented normal heart, 99Tc m/ 123I matched myocardium, 99Tc m/ 123I mismatched myocardium, respectively. Nineteen patients (9 males, 10 females; age (56±16) years) from September 2018 to June 2020 at Fuwai Hospital were enrolled to participate 99Tc m-MIBI myocardial perfusion imaging and myocardial perfusion/cardiac sympathetic imaging with 99Tc m-MIBI/ 123I-MIBG dual-isotope. Perfusion percent (PP%) and summed rest score (SRS) for all myocardial segments were obtained using quantitative perfusion SPECT (QPS) software by analyzing myocardial perfusion images. Difference and relationship between PP% and SRS were analyzed (Pearson and Spearman correlation analyses). No physical correction was applied for both acquisitions. Analysis of variance for repeated measurement data and Mann-Whitney U test were used. Results:There was no significant difference in myocardial perfusion images between 99Tc m single-isotope and 99Tc m/ 123I dual-isotope imaging with the heart phantom. 123I did not significantly impact on 99Tc m images. For patients, PP% did not differ between 99Tc m single-isotope ((69.2±14.5)%) and 99Tc m/ 123I dual-isotope imaging ((69.5±16.2)%; F=0.005, P=0.946) and correlated well ( r=0.845, P<0.01). SRS for 99Tc m single-isotope was 2(1, 13) and 2(2, 12) for 99Tc m/ 123I dual-isotope imaging ( z=-0.774, P=0.439) and the correlation between the two acquisitions was excellent ( rs=0.975, P<0.01). Conclusions:Even without physical correction, cardiac images interpretation won′t be significantly influenced by the interference of 123I with relatively higher energy on 99Tc m images. Cardiac 99Tc m-MIBI/ 123I-MIBG dual-isotope imaging is feasible.

Value of 123 I-MIBG SPECT/CT imaging in the diagnosis and treatment of pediatric neuroblastoma / 中华核医学与分子影像杂志

Objective To investigate the clinical value of 123I-metaiodobenzylguanidine (MIBG) SPECT/CT imaging in the diagnosis and treatment of pediatric patients with neuroblastoma ( NB) . Methods A total of 196 NB patients (103 males, 93 females;age 1-14 years) who underwent 123I-MIBG SPECT/CT imaging in Beijing Friendship Hospital between February 2018 and December 2018 were reviewed retrospec-tively. All patients underwent whole-body planar imaging and local SPECT/CT imaging. According to the clinical data and 123 I-MIBG imaging results, patients were divided into 3 groups ( group 1: patients under-went preoperative planar imaging; group 2: patients with positive results in postoperative planar imaging;group 3:patients with negative results in postoperative planar imaging). The final diagnosis was made ac-cording to pathological results, other related imaging results and clinical follow-up results. The diagnostic consistency between planar imaging or SPECT/CT imaging and final diagnosis in each group was calculated and compared using χ2 test. Results For group 1 ( n=34) , the diagnostic consistencies of planar imaging and SPECT/CT imaging with the final diagnosis were 38.2％(13/34) and 82.4％(28/34) respectively (χ2=13.82, P<0.01), while those were 13.3％(12/90) and 74.4％(67/90) for group 2 (n=90;χ2=68.24, P<0. 01). In these two groups, SPECT/CT imaging improved the planar imaging results by 44.12％(15/34) and 61.11％(55/90) respectively. For group 3 (n=72), the diagnostic consistencies of planar imaging and SPECT/CT imaging with the final diagnosis were 88.9％(64/72) and 94.4％(68/72;χ2=1.45, P>0.05), and planar imaging results in only 5.56％(4/72) patients were improved by SPECT/CT imaging. Conclu-sions For patients undergoing preoperative imaging and those with positive results in postoperative planar imaging, SPECT/CT imaging should be added. For patients with negative results in postoperative planar im-aging, unnecessary SPECT/CT imaging should be limited.

A Case of Malignant Pheochromocytoma Presenting 7 Years After the Initial Surgery.

BACKGROUND: Pheochromocytoma (PHEO) is a rare tumor of the adrenal medulla and sympathetic ganglion that produces the catecholamines norepinephrine and epinephrine. Traditionally, approximately 10% of PHEOs were thought to be malignant, but recent developments in PHEO research have noted that specific genetic mutations are associated with higher risk of metastatic spread. CASE REPORT: We report the case of a 71-year-old female who presented with abdominal pain in September 2009 when she was 64 years old. Evaluation at that time revealed cholelithiasis and bilateral adrenal masses. Workup showed elevated free normetanephrines, and positron emission tomography-computed tomography demonstrated bilateral adrenal hypermetabolic lesions concerning for malignancy. She underwent open bilateral adrenalectomies and cholecystectomy. The right adrenal mass was identified as a PHEO with nonaggressive features and negative margins, and the left adrenal mass was an adrenal cortical adenoma without dysplasia. In April 2016, the patient was referred by her endocrinologist for elevated blood pressure and 16-lb weight loss. The patient reported weakness, headaches, hot flashes, cold sweats, and fatigue. Laboratory workup revealed elevated plasma free normetanephrine, and imaging showed a recurrence of the PHEO in both the right adrenal bed and the head of the right humerus. CONCLUSION: Current predictors of PHEO recurrence failed to identify the original tumor as aggressive or likely to return as a metastatic lesion. Because of the rarity of these tumors, few consistent laboratory or radiologic predictors of malignancy based on initial presentation have been identified; predictors of malignancy in PHEO warrant further investigation.

Integrated Imaging Characterization of Adrenal Adenoma: False-Positive Metaiodobenzylguanidine (MIBG) Findings of Adrenal Scintigraphy.

BACKGROUND: Evaluation of a patient with melanoma in whom an adrenal mass was detected on CT and MR during follow-up and further characterized with PET-CT and MIBG scintigraphy. CASE REPORT: In this case report, we describe a patient with melanoma in whom an adrenal mass was detected on CT and MRI during post-surgical follow-up and was further characterized with radionuclide studies consisting of PET-CT and MIBG scintigraphy. Although the results of imaging studies suggested that the mass was a pheochromocytoma, a cortical adrenal adenoma was histologically proven. CONCLUSIONS: Integrated structural and functional imaging is recommended to characterize adrenal tumors; however, mistakes may occur and therefore careful imaging evaluation is required.

Application of 123/131I-MIBG in the diagnosis and treatment of pediatric neuroblastoma / 中华核医学与分子影像杂志

As a type of neuroendocrine tumors,neuroblastoma (NB) is the most common extra-cranial solid tumor of childhood.123/131I-MIBG scintigraphy is a standard imaging modality in staging and evaluating therapeutic effect of pediatric NB with high accuracy.131I-MIBG treatment is effective for children with high-risk and relapsed/refractory NB.Combined with chemotherapy,stem cell transplantation,131I-MIBG treatment shows efficacy in decreasing the relapse of pediatric NB.This review summarizes the application of MIBG scintigraphy and 131I-MIBG treatment for pediatric NB.

Application of 123/131I-MIBG in the diagnosis and treatment of pediatric neuroblastoma / 中华核医学与分子影像杂志

As a type of neuroendocrine tumors, neuroblastoma (NB) is the most common extra-cranial solid tumor of childhood.123/131I-MIBG scintigraphy is a standard imaging modality in staging and evaluating therapeutic effect of pediatric NB with high accuracy.131I-MIBG treatment is effective for children with high-risk and relapsed/refractory NB.Combined with chemotherapy, stem cell transplantation, 131I-MIBG treatment shows efficacy in decreasing the relapse of pediatric NB.This review summarizes the application of MIBG scintigraphy and 131I-MIBG treatment for pediatric NB.

Orthostatic hypotension and cognitive impairment in Parkinson's disease: Causation or association?

Orthostatic hypotension and cognitive impairment are common in Parkinson's disease (PD) and significantly impair quality of life. Orthostatic hypotension and cognitive impairment appear to be interrelated. Whether the relationship is causative or associative remains unclear. The vascular hypothesis proposes that recurrent episodic hypotension results in cerebral hypoperfusion, in turn causing anoxic damage to vulnerable areas of the brain and impaired cognitive function. Support for this hypothesis has come from brain MRI studies showing an association between white matter hyperintensities and a postural drop in blood pressure among PD patients. Alternatively, the association between orthostatic hypotension and cognitive decline in PD may reflect shared underlying synuclein-related pathology affecting common neuroanatomical and neurochemical substrates. Cardiac imaging studies demonstrate noradrenergic denervation early in PD, and cardiac denervation has been associated with poorer cognition. Neurogenic orthostatic hypotension occurs as a result of defective norepinephrine release from sympathetic terminals upon standing. Neuropathological studies have also demonstrated Lewy body pathology in the locus coeruleus; the main source of noradrenaline in the brain. Locus coeruleus norepinephrine levels are reduced in PD patients with dementia when compared with PD patients without. In this review, we examine the evidence for an association between orthostatic hypotension and cognitive impairment in PD. We evaluate the literature supporting the hypothesis that progressive noradrenergic denervation underlies both orthostatic hypotension and cognitive impairment, and we examine studies suggesting that recurrent cerebral hypoperfusion results in cognitive decline in PD. Finally, we explore how modulation of blood pressure and the noradrenergic nervous system may improve cognition in PD. © 2016 International Parkinson and Movement Disorder Society.

Cardiac 123I-MIBG uptake in de novo Brazilian patients with Parkinson's disease without clinically defined dysautonomia / Cintilografia Miocárdica com 123I-MIBG em pacientes brasileiros com doença de Parkinson recentemente diagnosticada sem disautonomia clinicamente manifesta

Myocardial scintigraphy with meta-iodo-benzyl-guanidine (123I cMIBG) has been studied in Parkinson's disease (PD), especially in Asian countries, but not in Latin America. Most of these studies include individuals with PD associated to a defined dysautonomia. Our goal is to report the cardiac sympathetic neurotransmission in de novo Brazilian patients with sporadic PD, without clinically defined dysautonomia. We evaluated retrospectively a series of 21 consecutive cases with PD without symptoms or signs of dysautonomia assessed by the standard bedside tests. This number was reduced to 14 with the application of exclusion criteria. 123I cMIBG SPECT up-take was low or absent in all of them and the heart/mediastinum ratio was low in 12 of 14. We concluded that 123I cMIBG has been able to identify cardiac sympathetic neurotransmission disorder in Brazilian de novo PD patients without clinically defined dysautonomia.

A cintilografia miocárdica com meta-iodo-benzil-guanidina (123I cMIBG) foi estudada na doença de Parkinson (DP), especialmente nos países asiáticos, mas não na América Latina. A quase totalidade desses estudos inclui indivíduos com DP com disautonomia definida. Nosso objetivo é relatar a neurotransmissão simpática cardíaca em doentes brasileiros com DP de novo esporádica, sem disautonomia clinicamente definida. Foi avaliada retrospectivamente uma série de 21 casos consecutivos com DP sem sintomas ou sinais de disautonomia observáveis pelos testes de beira-de-leito. Com a aplicação dos critérios de exclusão, este número foi reduzido para 14. A captação do 123I MIBG pelo SPECT foi baixa ou ausente em todos os pacientese; a relação coração / mediastino foi baixa em 12 dos 14. Concluímos que a 123c MIBG é capaz de identificar alteração da neurotransmissão simpática cardíaca em doentes com DP de novo sem disautonomia clinicamente definida.

An 85-year old male with levodopa-responsive parkinsonism followed by dementia and supranuclear ophthalmoplegia caused by alzheimer-type pathology without Lewy bodies.

An 85-year-old man developed l-dopa responsive parkinsonism indistinguishable from Parkinson's disease and subsequent dementia, followed by supranuclear ophthalmoplegia and neck dorsiflexion at the terminal stage. Midbrain tegmentum and medial temporal lobe were atrophic on magnetic resonance imaging, while decreased blood flow was predominant in frontotemporal lobes, detected by 3D-SSP of 123I- IMP SPECT. Alzheimer-type pathology without Lewy body pathology was confirmed at autopsy. Substantia nigra showed mild degeneration and several neurofibrillary tangles without Lewy body pathology or progressive supranuclear palsy cytopathology. L-dopa responsive parkinsonism could be an initial manifestation of Alzheimer's disease, which should be included in the differential diagnosis.

O I123-MIBG cardíaco se correlaciona melhor do que a fração de ejeção com a gravidade dos sintomas na insuficiência cardíaca sistólica / Cardiac I123-MIBG correlates better than ejection fraction with symptoms severity in systolic heart failure

FUNDAMENTO: A associação da ativação autonômica, fração de ejeção do ventrículo esquerdo (FEVE) e classe funcional da insuficiência cardíaca é mal compreendida. Objetivo: Nosso objetivo foi correlacionar a gravidade dos sintomas com a atividade simpática cardíaca, através do uso de iodo-123-metaiodobenzilguanidina (123I-MIBG); e com FEVE em pacientes com insuficiência cardíaca (IC) sistólica sem tratamento prévio com betabloqueador. MÉTODOS: Trinta e um pacientes com IC sistólica, classe I a IV da New York Heart Association (NYHA), sem tratamento prévio com betabloqueador, foram inscritos e submetidos à cintilografia com 123I-MIBG e ventriculografia radioisotópica para determinação da FEVE. A relação precoce e tardia coração/mediastino (H/M) e a taxa de washout (WO) foram medidas. RESULTADOS: De acordo com a gravidade dos sintomas, os pacientes foram divididos em grupo A, com 13 pacientes em classe funcional NYHA I/II, e grupo B, com 18 pacientes em classe funcional NYHA III/ IV. Em comparação com os pacientes do grupo B, o grupo A apresentou uma FEVE significativamente maior (25% ± 12% para o grupo B vs. 32% ± 7% no grupo A, p = 0,04). As relações precoces e tardias H/M do Grupo B foram menores do que as do grupo A (H/M precoce 1,49 ± 0,15 vs. 1,64 ± 0,14, p = 0,02; H/M tardia 1,39 ± 0,13 vs. 1,58 ± 0,16, p = 0,001, respectivamente). A taxa de WO foi significativamente maior no grupo B (36% ± 17% vs. 30% ± 12%, p = 0,04). A variável que mostrou a melhor correlação com a NYHA foi a relação H/M tardia (r = -0,585, p = 0,001), ajustada para idade e sexo. CONCLUSÃO: Esse estudo mostrou que o 123I-MIBG cardíaco se correlaciona melhor do que a fração de ejeção com a gravidade dos sintomas em pacientes com insuficiência cardíaca sistólica sem tratamento prévio com beta-bloqueador.

BACKGROUND:The association of autonomic activation, left ventricular ejection fraction (LVEF) and heart failure functional class is poorly understood. OBJECTIVE: Our aim was to correlate symptom severity with cardiac sympathetic activity, through iodine-123-metaiodobenzylguanidine (123I-MIBG) scintigraphy and with LVEF in systolic heart failure (HF) patients without previous beta-blocker treatment. METHODS: Thirty-one patients with systolic HF, class I to IV of the New York Heart Association (NYHA), without previous beta-blocker treatment, were enrolled and submitted to 123I-MIBG scintigraphy and to radionuclide ventriculography for LVEF determination. The early and delayed heart/mediastinum (H/M) ratio and the washout rate (WR) were performed. RESULTS: According with symptom severity, patients were divided into group A, 13 patients in NYHA class I/II, and group B, 18 patients in NYHA class III/IV. Compared with group B patients, group A had a significantly higher LVEF (25% ± 12% in group B vs. 32% ± 7% in group A, p = 0.04). Group B early and delayed H/M ratios were lower than group A ratios (early H/M 1.49 ± 0.15 vs. 1.64 ± 0.14, p = 0.02; delayed H/M 1.39 ± 0.13 vs. 1.58 ± 0.16, p = 0.001, respectively). WR was significantly higher in group B (36% ± 17% vs. 30% ± 12%, p= 0.04). The variable that showed the best correlation with NYHA class was the delayed H/M ratio (r= -0.585; p=0.001), adjusted for age and sex. CONCLUSION: This study showed that cardiac 123I-MIBG correlates better than ejection fraction with symptom severity in systolic heart failure patients without previous beta-blocker treatment.

Interleucina 1β correlaciona-se com MIBG e parâmetros do exercício, na insuficiência cardíaca? / Do interleukin-1β levels correlate with MIBG and exercise parameters in heart failure?

FUNDAMENTO: Na insuficiência cardíaca, níveis de interleucina 1β (IL 1β) se associam a prognóstico. A atividade adrenérgica cardíaca avaliada através da cintilografia com metiodobenzilguanidina (I123 MIBG) e parâmetros do exercício são importantes preditores de prognóstico. A relação entre essas variáveis não está bem definida. OBJETIVO: Avaliar associação entre níveis de IL 1β com parâmetros do exercício e do I123 MIBG. MÉTODOS: Estudo observacional transversal, com avaliação de 25 pacientes consecutivos com insuficiência cardíaca e fração de ejeção menor que 45%, através de: dosagem de IL 1β; parâmetros do I123 MIBG [relação coração/mediastino precoce e tardia, taxa de washout (WO)]; e teste ergométrico em esteira pelo protocolo de Rampa. RESULTADOS: Separados em dois grupos pelos níveis de IL 1β (normal vs. elevado), o grupo com níveis aumentados apresentava menor reserva de duplo produto (RDP), menor capacidade funcional (CF) e recuperação mais lenta da frequência cardíaca no 1º (RFC 1º) e 2º minuto (RFC 2º), e maior WO. Na análise univariada, todas as variáveis se correlacionaram com a IL 1β; RDP: r = 0,203, p = 0,024; CF: r = 0,181, p = 0,034; RFC 1º: r = 0,182, p = 0,034; RFC 2º: r = 0,204, p = 0,023; WO: r = 0,263, p = 0,009. Na multivariada, apenas a WO permaneceu com correlação significativa (r2 = 0,263, p = 0,009). CONCLUSÃO: A hipertonia adrenérgica foi o principal determinante dos níveis de IL 1β, demonstrando que a atividade simpática excessiva influencia a atividade inflamatória sistêmica. As variáveis do teste ergométrico não foram capazes de identificar pacientes com níveis elevados de IL 1β.

BACKGROUND: Interleukin 1β (IL 1β) levels are associated with prognosis in heart failure. The cardiac adrenergic activity as assessed by metaiodobenzylguanidine (I123 MIBG) scintigraphy along with exercise parameters are important predictors of prognosis. The relationship between these variables is not fully established. OBJECTIVE: To evaluate the association of IL 1β levels with exercise and I123 MIBG parameters. METHODS: Cross-sectional observational study evaluating 25 consecutive patients with heart failure and ejection fraction lower than 45% by means of: determination of IL 1β levels; I123 MIBG parameters [early and late heart/mediastinum ratio, washout rate (WO)]; and treadmill exercise test using the ramp protocol. RESULTS: The patients were divided into two groups according to their IL 1β levels (normal vs. increased). The group with increased levels showed lower double-product reserve (DPR); lower functional capacity (FC); slower heart rate recovery at the first (HRR 1º) and second minute (HRR 2º); and higher WO. In the univariate analysis, all variables correlated with IL 1β; DPR: r = 0.203, p = 0.024; FC: r = 0.181, p = 0.034; HRR 1º: r = 0.182, p = 0.034; HRR 2º: r = 0.204, p = 0.023; WO: r = 0.263, p = 0.009. In the multivariate analysis, only WO maintained a significant correlation (r² = 0.263, p = 0.009). CONCLUSION: Adrenergic overactivity was the main determinant of IL 1β levels, thus demonstrating that an excessive sympathetic activity influences the systemic inflammatory response. Exercise test variables were not able to identify patients with high IL 1β levels.

Depicting medullary thyroid cancer recurrence: the past and the future of nuclear medicine imaging.

CONTEXT: Inherited and sporadic medullary thyroid cancer (MTC) is an uncommon and medically challenging malignancy. Even if the extent of initial surgery is deemed adequate, the recurrence rate remains high, up to 50% in most series. Measurement of serum calcitonin is important in the follow-up of patients with MTC, and reliably reflects the existence of the disease. EVIDENCE ACQUISITION: There is no single sensitive diagnostic imaging method to reveal all MTC recurrences or metastases. Conventional morphologic imaging methods (U/S, CT, and MRI) and several methods of nuclear medicine have been used for this purpose with variable accuracy. RESULTS: The main role of nuclear medicine imaging is the detection of residual or recurrent tumor in the postoperative follow-up. In this review we present the radiopharmaceuticals used in the diagnosis of MTC recurrence, and comparison among them. CONCLUSIONS: The most used radiopharmaceuticals labelled with γ emitters are: Metaiodobenzylguanidine (MIBG), labelled with (131)I or (123)I, (111)In-pentetreotide (Octreoscan), 99mTc-pentavalent dimercaptosuccinic acid ((99m)Tc(V)-DMSA), and (99m)Tc-EDDA/HYNIC-Tyr3-Octreotide ( Tektrotyd). The radiopharmaceuticals labelled with a positron-emitting radionuclide (ß+), suitable for positron emission tomography (PET) imaging are: (18)F-fluorodeoxyglucose ((18)F-FDG), (18)F-fluorodihydroxyphenylalanine (18F-DOPA), and 68Ga-labelled somatostatin analogues (68Ga-DOTATATE or DOTATOC).

A Case of Paroxysmal Pheochromocytoma with Normal Catecholamine Levels / 대한내과학회지

A 53-year-old woman had a 1.7 cm left adrenal mass on an abdominal computed tomography (CT) scan. She presented with paroxysmal headache, palpitation, sweating, and hypertension. The patient was highly suspected of having a pheochromocytoma, but measurements of 24-hour urinary metanephrine, catecholamines, and vanillylmandelic acid were normal. Plasma and urine catecholamine levels were within the normal range even during paroxysmal episodes. A scintigraphic study with 131I-metaiodobenzylguanidine (MIBG) revealed selective concentration of the radiotracer, corresponding to the CT mass. The patient underwent a left adrenalectomy and the pathological examination confirmed the diagnosis of pheochromocytoma. In this report, we describe a rare case of a symptomatic pheochromocytoma with normal catecholamine levels. Our case illustrates that routine nuclear scintigraphy, such as 131I-MIBG, should be performed even in cases with normal hormonal testing for all patients with high clinical suspicion of pheochromocytoma.

Efeito do carvedilol a curto prazo na atividade simpática cardíaca pela cintilografia com 123I-MIBG / Effects of short-term carvedilol on the cardiac sympathetic activity assessed by 123I-MIBG scintigraphy

FUNDAMENTO: Alterações autonômicas na insuficiência cardíaca estão associadas a um aumento da morbimortalidade. Vários métodos não invasivos têm sido empregados para avaliar a função simpática, incluindo a imagem cardíaca com 123I-MIBG. OBJETIVO: Avaliar a atividade simpática cardíaca, por meio da cintilografia com 123I-MIBG, antes e após três meses de terapia com carvedilol em pacientes com insuficiência cardíaca com fração de ejeção do VE <45 por cento (FEVE). MÉTODOS: Foram recrutados para o estudo 16 pacientes, com idade média de 56,3 ± 12,6 anos (11 do sexo masculino), fração de ejeção média de 28 por cento ± 8 por cento e sem uso prévio de betabloqueadores. Realizaram-se imagens da inervação cardíaca com 123I-MIBG, determinando os níveis séricos de catecolaminas (epinefrina, dopamina e norepinefrina), e empreendeu-se a ventriculografia radionuclídica antes e após o uso de carvedilol por três meses. RESULTADOS: Houve melhora da classe funcional dos pacientes: antes do tratamento, metade se encontrava em CF II (50 por cento) e metade em CF III. Após 3 meses, 7 pacientes encontravam-se em CF I (43,8 por cento) e 9 em CF II (56,2 por cento), (p = 0,0001). A FEVE média avaliada pela ventriculografia radionuclídica aumentou de 29 por cento para 33 por cento (p = 0,017). Não houve variação significativa da atividade adrenérgica cardíaca avaliada pelo 123I-MIBG (imagem precoce, tardia e taxa de washout). Não foi observada variação significativa nas dosagens das catecolaminas. CONCLUSÃO: O tratamento em curto prazo com carvedilol promoveu a melhora clínica e da FEVE. Entretanto, não foi associado à melhora da atividade adrenérgica cardíaca pela cintilografia com 123I-MIBG, bem como da dosagem das catecolaminas circulantes.

BACKGROUND: Autonomic alterations in heart failure are associated with an increase in morbimortality. Several noninvasive methods have been employed to evaluate the sympathetic function, including the Meta-Iodobenzylguanidine (123I-MIBG) scintigraphy imaging of the heart. OBJECTIVE: to evaluate the cardiac sympathetic activity through 123I-MIBG scintigraphy, before and after three months of carvedilol therapy in patients with heart failure and left ventricular ejection fraction (LVEF) < 45 percent. PATIENTS AND METHODS: Sixteen patients, aged 56.3 ± 12.6 years (11 males), with a mean LVEF of 28 percent ± 8 percent and no previous use of beta-blockers were recruited for the study. Images of the heart innervation were acquired with 123I-MIBG, and the serum levels of catecholamines (epinephrine, dopamine and norepinephrine) were measured; the radioisotope ventriculography (RIV) was performed before and after a three-month therapy with carvedilol. RESULTS: Patients' functional class showed improvement: before the treatment, 50 percent of the patients were FC II and 50 percent were FC III. After 3 months, 7 patients were FC I (43.8 percent) and 9 were FC II (56.2 percent), (p = 0.0001). The mean LVEF assessed by RIV increased from 29 percent to 33 percent (p = 0.017). There was no significant variation in cardiac adrenergic activity assessed by 123I-MIBG (early and late resting images and washout rate). No significant variation was observed regarding the measurement of catecholamines. CONCLUSION: The short-term treatment with carvedilol promoted the clinical and LVEF improvement. However, this was not associated to an improvement in the cardiac adrenergic activity, assessed by 123I-MIBG scintigraphy, as well as the measurement of circulating catecholamines.

Application of 131I-MIBG scintigraphy in diagnosis of pheochromocytoma / 中国医学影像技术

Objective To assess the clinical value of 131I-metaiodobenzylguanidine (MIBG) scintigraphy in pheochromocytoma. Methods A total of 430 patients with clinically suspected pheochromocytoma underwent 131I-MIBG whole body scintigraphy, 326 among them underwent B-ultrasound, 400 for CT and 77 for MR examination respectively. While 178 among them were diagnosed with pathology and the others were diagnosed clinically. Results Of all the patients, 108 were diagnosed pheochromocytoma, including 89 131I-MIBG scan positive and 19 negative. The sensitivity, specificity and accuracy of 131I-MIBG were 82.41%, 100% and 95.70%, respectively. 131I-MIBG scan detected 90.00% of unilateral adrenal, 45.45% of bilateral adrenal, 85.71% of ectopic and 66.67% of malignant lesions, respectively. The proportion of patients with positive 131I-MIBG scan increased from 20.69% in all patients to 35.15% in patients with clinical symptoms and positive conventional imaging (at least one of B-ultrasonography, CT or MR was positive) and 64.58% in those with clinical symptoms, positive conventional imaging, and elevated 24 h urinary catacholamines. In 59 patients with adrenal incidentaloma, 8 were scan-positive and all had confirmed pheochromocytoma, while 2 of scan-negative patients also had confirmed pheochromocytoma. Conclusion 131I-MIBG scintigraphy is the first choice for the diagnosis of both adrenal and extra-adrenal pheochromocytoma. However, it is inappropriate to take this method as the initial screening approach.

Olfactory Function and Its Correlation with Cardiac 123I-MIBG in Patients with Parkinson's Disease and Multiple System Atrophy

BACKGROUND: Olfactory dysfunction is common in patients with Parkinsons disease (PD) and may precede the development of parkinsonian motor symptoms. Cardiac sympathetic denervation, which can be visualized by a cardiac (123)I-metaiodobenzylguanidine (MIBG) scan, is common in patients with PD. In this study, we evaluated olfactory functions in patients with IPD and MSA, and investigated an association between olfaction and cardiac 123I-MIBG uptake in these patients. METHODS: We prospectively enrolled 26 patients with PD, 19 patients with MSA, and 18 healthy controls. Olfactory function was evaluated with a 12-Item Cross-Cultural Smell Identification Test (CC-SIT) and Butanol threshold. 123I-MIBG (111 mBq) was injected intravenously into each subject, and cardiac uptake was imaged 3 hours later. The regions of interest were the whole heart and the mediastinum of the front image, and the ratio of 123I-MIBG uptake in the heart to that in the mediastinum (H/M ratio) was calculated. The clinical stages of parkinsonism were assessed according to the classification of Hoehn and Yahr (H&Y) and the Unified PD Rating Scale (UPDRS). RESULTS: The mean CC-SIT score in patients with PD was 4.4+/-2.2, which was significantly lower than that in patients with MSA (6.7+/-2.0) or in controls (7.3+/-2.6). There was a significant positive correlation between cardiac 123I-MIBG uptake and the CC-SIT score in patients with PD (r=0.56, p=0.003). Neither the CC-SIT score nor cardiac 123I-MIBG uptake were significantly correlated with the disease duration, the H&Y stage or motor UPDRS score. In the patients with MSA, the CC-SIT and cardiac 123I-MIBG uptake did not show a significant correlation with age (r=0.01 and r=0.11, each p>0.05), and they were not significantly correlated with each other (r=0.01, p>0.05). CONCLUSIONS: Our data suggest that the functional loss of the olfactory and cardiac sympathetic systems is closely coupled in PD.

A case of metastatic malignant pheochromocytoma response to high dose 131I-MIBG treatment after surgery / 대한내과학회지

Approximately 10% of pheochromocytomas are malignant and its major criteria are tumor invasion of capsular blood vessel as well as metastatic invasion of other tissues. It is general rule that all resectable masses have to be removed surgically. However, there is no definite treatment modality about unresectable masses or microinvasive lesions. We experienced a case of 45 year-old male patient who was referred to our hospital for treatment of hypertension and headache. The plasma and urine catecholamine were increased above normal values and its metabolites also were increased. 131I-metaiodobenzylguanidine (MIBG) scan showed right adrenal mass and metastatic lesion of left iliac bone. This lesion was consistent with findings of the abdomen computed tomography (CT) and electron beam tomography (EBT) scan. We diagnosed this case as malignant pheochromocytoma. We removed primary tumor mass by wide excision and treated this patient with high dose 131I-MIBG. We report this case who shows good response to the high dose 131I-MIBG after surgery.