The clinical value of 123I-metaiodobenzylguanidine myocardial imaging in the diagnosis of dementia with Lewy bodies / 生物医学工程学杂志

Metaiodobenzylguanidine (MIBG) is an analog of norepinephrine that accumulates in sympathetic nerve endings soon after intravenous administration. The degree of accumulation reflects the uptake, storage and release of transmitters by noradrenergic neurons. Myocardial imaging with 123I labeled MIBG ( 123I-MIBG) can be used to estimate the extent of local myocardial sympathetic nerve damage, which has been widely used in the diagnosis and treatment of various heart diseases. In recent years, numerous studies have been carried out on the application of 123I-MIBG in the diagnosis of degenerative diseases of the nervous system (such as Parkinson's disease and dementia of Lewy body), and have made some achievements. The purpose of this review is to summarize the current clinical application of 123I-MIBG myocardial imaging in the diagnosis of dementia with Lewy bodies, the problems in imaging technology and the possible research directions in the future, so as to provide valuable reference information for clinicians to reasonably and accurately apply this technology in the early diagnosis and discrimination of dementia.

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.

The Role of I-131 MIBG cardiac scintigraphy in diagnosing dementia with lewy bodies : A case report

@#The objective of this case report is to highlight the role of Iodine-131 metaiodobenzylguanidine (MIBG) cardiac scintigraphy in discriminating Dementia with Lewy Bodies (DLB) from other neurodegenerative diseases such as Alzheimer’s Disease. This patient is a known case of Parkinson’s disease and has been treated as such since 2011. However, the patient also concurrently deals with visual hallucinations and because of this, the patient’s attending neurologist wanted to rule in the diagnosis of DLB rather than AD. Hence, an I-131 MIBG cardiac scan was requested in order to support the diagnosis of DLB. The use of I-131 MIBG cardiac scintigraphy as a diagnostic tool for diagnosing Lewy Body Dementia is not prevalent and to our knowledge, this was the first time in the country that this procedure was done (December 9, 2019).

Disfunción tiroidea por I131-Metayodo Benzilguanidina en pacientes con neuroblastoma / Thyroid dysfunction due to 131I-metaiodobenzylguanidine in patients with neuroblastoma

Resumen: Introducción: El tratamiento del neuroblastoma en estadios avanzados incluye quimioterapia, cirugía y terapia con I131-Metayodo benzilguanidina (I131-MIBG). La disfunción tiroidea se reporta entre 12 y 85% a pesar de la protección tiroidea. Objetivo: Identificar la frecuencia de disfunción tiroidea en casos de neu roblastoma tratados con I131-MIBG. Pacientes y Método: Estudio transversal. Se incluyeron todos los casos con diagnóstico de neuroblastoma que recibieron I131-MIBG en el periodo de 2002-2015, a los cuales se les realizó antropometría completa, perfil de tiroides: hormona estimulante de tiroides (TSH), Triyodotironina total y libre (T3t y T3l), tiroxina total y libre (T4t, T4l), y anticuerpos antitiroglobulina y antiperoxidasa. Resultados: Se identificaron un total de 27 pacientes; once fallecieron (40%). De los 16 casos sobrevivientes, 9 (56%) presentaron disfunción tiroidea: 2 (13%) casos con hipotiroidismo subclínico y 7 (44%) casos con hipotiroidismo clínico (3 casos por retraso en el desa rrollo psicomotor y 4 por desaceleración del crecimiento). Los pacientes presentaron manifestaciones clínicas a los 16,1 meses (1,2-66,3 meses) de recibir el radiofármaco a una dosis acumulada de 142 mCi (96-391.5 mCi). No se logró evidenciar diferencias en la edad al diagnóstico, la edad al inicio del tratamiento con el I131-MIBG, la dosis acumulada del I131-MIBG y el tiempo trascurrido entre la dosis y el perfil tiroideo entre los casos con o sin disfunción tiroidea. Conclusiones: El 56% de los pacientes con neuroblastoma presentaron disfunción tiroidea. La mayoría de los casos con hipotiroidismo fue ron referidos cuando los datos de disfunción tiroidea eran clínicamente evidentes. Se propone en esta poblacion realizar perfil tiroideo semestral y valoración anual por un endocrinólogo pediatra durante los primeros 5 años posteriores al diagnóstico oncológico.

Abstract: Introduction: The treatment of advanced neuroblastoma includes chemotherapy, surgery, and radiotherapy with 131-I-Metaiodobenzylguanidine (131-I-MIBG). Despite strategies to protect thyroid function, its dysfunction is reported between 12 and 85%. Objective: To identify the frequency of thyroid dys function in cases of neuroblastoma treated with 131-I-MIBG. Patients and Method: Cross-sectional study. We included all the cases with neuroblastoma treated with 131-I-MIBG between 2002 and 2015, with complete somatometry, and complete thyroid profile (TSH, free and total T3 and T4, and anti-thyroglobulin and antiperoxidase antibodies). Results: 27 patients were identified out of which eleven died (40%). Out of the 16 surviving cases, 9 (56%) presented thyroid dysfunction: 2 (13%) cases with subclinical hypothyroidism and 7 (44%) cases with clinical hypothyroidism (3 cases due to psychomotor developmental delay and 4 due to growth deceleration). The patients presented cli nical manifestations at 16.1 months (1.2-66.3 months) after receiving the radiopharmaceutical at acumulative dose of 142 mCi (96-391.5 mCi). No differences were found in the age at diagnosis, age at the start of treatment with 131-I-MIBG, the cumulative dose of 131-I-MIBG, and the time elapsed between the dose and the thyroid profile among the cases with or without thyroid dysfunction. Con clusions: 56% of patients with neuroblastoma had thyroid dysfunction. Most of the cases with hypothyroidism were referred when thyroid dysfunction was clinically evident. A thyroid profile should be performed every 6 months, along with an annual endocrinological evaluation during the next 5 years in these patients.

Nuclear Theranostics in Turkey / 대한핵의학회잡지

Nuclear theranostics functions as a bridge which connects targeted diagnosis to targeted therapy, just like Turkey functions as a geographical bridge which connects Asia to Europe. This unique geographical site of the country plays an important role with regard to introduction of novel scientific and technologic improvements, which originate from one continent to another, in the era of accelerated information. The first nuclear medicine practice in Turkey started in the beginning of 1950s with the first radioiodine treatment, which actually was a debut for nuclear theranostics in Turkey, years before many other countries in the world. For the time being, along with radioiodine treatment, many other theranostic applications such as I-131 MIBG treatment, Lu-177/Y-90 DOTA peptide treatment, Lu-177 PSMA treatment, Y-90 microsphere treatment, and bone palliative treatment are being performed in many centers countrywide. As science and technology improves, novel theranostic applications are eagerly awaited to be introduced in near future. This paper summarizes the story of nuclear theranostics in Turkey and aims to give an overview on the current status of theranostic applications in Turkey.

Sympathetic Dysautonomia in Heart Failure by 123I-MIBG: comparison between Chagasic, non-Chagasic and heart transplant patients / Disautonomia Simpática na Insuficiência Cardíaca pela 123I-MIBG: Comparação entre Pacientes Chagásicos, não-Chagásicos e Transplantados Cardíacos

Abstract Background: Heart failure (HF) is a severe public health problem because of its high morbidity and mortality and elevated costs, thus requiring better understanding of its course. In its complex and multifactorial pathogenesis, sympathetic hyperactivity plays a relevant role. Considering that sympathetic dysfunction is already present in the initial phases of chronic Chagas cardiomyopathy (CCC) and frequently associated with a worse prognosis, we assumed it could be more severe in CCC than in cardiomyopathies of other etiologies (non-CCC). Objectives: To assess the cardiac sympathetic dysfunction 123I-MIBG) of HF, comparing individuals with CCC to those with non-CCC, using heart transplant (HT) patients as denervated heart parameters. Methods: We assessed 76 patients with functional class II-VI HF, being 25 CCC (17 men), 25 non-CCC (14 men) and 26 HT (20 men), by use of cardiac 123I-metaiodobenzylguanidine 123I-MIBG) scintigraphy, estimating the early and late heart-to-mediastinum ratio (HMR) of 123I-MIBG uptake and cardiac washout (WO%). The 5% significance level was adopted in the statistical analysis. Results: The early and late HMR values were 1.73 ± 0.24 and 1.58 ± 0.27, respectively, in CCC, and 1.62 ± 0.21 and 1.44 ± 0.16 in non-CCC (p = NS), being, however, higher in HT patients (p < 0.001). The WO% values were 41.65 ± 21.4 (CCC), 47.37 ± 14.19% (non-CCC) and 43.29 ± 23.02 (HT), p = 0.057. The late HMR values showed a positive weak correlation with left ventricular ejection fraction (LVEF) in CCC and non-CCC (r = 0.42 and p = 0.045; and r = 0.49 and p = 0.015, respectively). Conclusion: Sympathetic hyperactivity 123I-MIBG) was evidenced in patients with class II-IV HF, LVEF < 45%, independently of the HF etiology, as compared to HT patients.

Resumo Fundamentos: A insuficiência cardíaca (IC) representa um grave problema de saúde pública pela alta morbimortalidade e custos envolvidos, exigindo uma melhor compreensão de sua evolução. Em sua patogênese, complexa e multifatorial, a hiperatividade simpática ocupa relevante papel. Considerando que a disfunção simpática está presente já nas fases iniciais da cardiopatia chagásica crônica (CCC), frequentemente associando-se a um pior prognóstico, supomos que pudesse ser mais grave na CCC que nas demais etiologias (não-CCC). Objetivos: Avaliar a disfunção simpática cardíaca (123I-MIBG) da IC, comparando-se os portadores de CCC aos não-CCC, utilizando os pacientes transplantados cardíacos (TC) como parâmetro de coração desnervado. Métodos: Estudamos 76 pacientes com IC classe funcional II-VI, sendo 25 CCC (17 homens), 25 não-CCC (14 homens) e 26 TC (20 homens), pela cintilografia cardíaca (123I-MIBG), estimando-se a captação (HMR) precoce e tardia e o washout cardíaco (Wc%). Nas análises estatísticas, o nível de significância foi de 5%. Resultados: Os valores da HMR precoce e da tardia foram 1,73 ± 0,24 e 1,58 ± 0,27, respectivamente, na CCC, e 1,62 ± 0,21 e 1,44 ± 0,16 na não-CCC (p = NS), sendo, porém, mais elevados nos TC (p < 0,001). Os valores de Wc% foram 41,65 ± 21,4 (CCC), 47,37 ± 14,19% (não-CCC) e 43,29 ± 23,02 (TC), p = 0,057. Os valores de HMR tardia apresentaram correlação positiva fraca com a fração de ejeção de ventrículo esquerdo (FEVE) na CCC e na não-CCC (r = 0,42 e p = 0,045; e r = 0,49 e p = 0,015, respectivamente). Conclusão: Evidenciou-se a presença de hiperatividade simpática (123I-MIBG) em pacientes com IC classe II-IV, FEVE < 45%, independentemente da etiologia da IC, quando comparados aos pacientes TC.

Value of SPECT/CT in Diagnostic I-131 MIBG Scintigraphy in Patients with Neuroblastoma / 대한핵의학회잡지

PURPOSE: Diagnostic I-131 MIBG scintigraphy is an important imaging modality for evaluation of patients with neuroblastoma (NB) especially in centers where I-123 MIBG is not available. Single photon emission computed tomography/computed tomography (SPECT/CT) could potentially improve lesion detection over planar scintigraphy, but studies regarding its usefulness as an add-on to diagnostic I-131 MIBG scintigraphy are limited. This study aimed to determine the usefulness and factors related to usefulness of SPECT/CT in diagnostic I-131 MIBG scintigraphy in NB patients.METHODS: Usefulness of SPECT/CT for lesion detection, lesion localization, resolving suspicious findings, and clarifying the nature of lesions on anatomical imaging were retrospectively reviewed in 86 diagnostic planar I-131 MIBG scintigrams with add-on SPECT/CT.RESULTS: SPECT/CT detected additional lesions in 23.2%(20/86), helped localize lesions in 21.1%(8/38), resolved suspicious findings in 85.7%(6/7), determined functional status of lesions on anatomical imaging in 94.4%(17/18), and changed diagnosis from a negative to a positive study in 19.5%(8/41). Independent predictors of SPECT/CT being useful included presence of suspicious findings on planar imaging (OR 99.08; 95% C.I. 6.99–1404.41; p = 0.001), positive findings on planar imaging (OR 4.61; 95% C.I. 1.05, 20.28; p < 0.001), and presence of structural lesions on anatomical imaging (OR 32.54; 95% C.I. 5.37–196.96; p < 0.001).CONCLUSION: SPECT/CT is a useful add-on to diagnostic planar I-131 MIBG scintigraphy. Predictors of usefulness of SPECT/CT include suspicious or positive findings on planar scintigraphy and the presence of structural lesions on anatomical imaging.

Current Consensus on I-131 MIBG Therapy / 대한핵의학회잡지

Metaiodobenzylguanidine (MIBG) is structurally similar to the neurotransmitter norepinephrine and specifically targets neuroendocrine cells including some neuroendocrine tumors. Iodine-131 (I-131)-labeled MIBG (I-131 MIBG) therapy for neuroendocrine tumors has been performed for more than a quarter-century. The indications of I-131 MIBG therapy include treatment-resistant neuroblastoma (NB), unresectable or metastatic pheochromocytoma (PC) and paraganglioma (PG), unresectable or metastatic carcinoid tumors, and unresectable or metastatic medullary thyroid cancer (MTC). I-131 MIBG therapy is one of the considerable effective treatments in patients with advanced NB, PC, and PG. On the other hand, I-131 MIBG therapy is an alternative method after more effective novel therapies are used such as radiolabeled somatostatin analogs and tyrosine kinase inhibitors in patients with advanced carcinoid tumors and MTC. No-carrier-aided (NCA) I-131 MIBG has more favorable potential compared to the conventional I-131 MIBG. Astatine-211-labeled meta-astatobenzylguanidine (At-211 MABG) has massive potential in patients with neuroendocrine tumors. Further studies about the therapeutic protocols of I-131 MIBG including NCA I-131 MIBG in the clinical setting and At-211 MABG in both the preclinical and clinical settings are needed.

Uso do 123I-mIBG Cardíaco na Rotina Clínica: A Necessidade de Padronizar! / The use of Cardiac123 I-mIBG Scintigraphy in Clinical Practice: The Necessity to Standardize!

A avaliação da atividade adrenérgica cardíaca através de exames de imagem apresenta grande potencial em uma ampla variedade de aplicações clínicas. A cintilografia miocárdica com 123I-mIBG desempenha papel importante na avaliação de insuficiência cardíaca crônica (ICC) ao estratificar o risco de pacientes para eventos cardíacos. A mIBG, um análogo da norepinefrina (NE), pode ser utilizada para avaliar a atividade simpática cardíaca ao se analisar a diminuição da expressão do adrenorreceptor (AR) ß na ICC. Além disso, a cintilografia miocárdica com 123I-mIBG em combinação com outros parâmetros de função ventricular esquerda pode ser usada para identificar o melhor respondedor a dispositivos cardíacos implantáveis, assim como avaliar cardiotoxicidade oncológica. Ainda que útil, a cintilografia miocárdica com 123I-mIBG não é amplamente realizada devido à falta de padronização entre as diferentes instituições. Portanto, sua padronização e validação podem contribuir para sua aceitação na prática clínica

Clinical Significance of Pretreatment FDG PET/CT in MIBG-Avid Pediatric Neuroblastoma / 대한핵의학회잡지

PURPOSE: ¹⁸F-fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging is well known to have clinical significance in the initial staging and response evaluation of the many kinds of neoplasms. However, its role in the pediatric neuroblastoma is not clearly defined. In the present study, the clinical significance of FDG-PET/computed tomography (CT) in ¹²³I- or ¹³¹I-metaiodobenzylguanidine (MIBG)-avid pediatric neuroblastoma was investigated.METHODS: Twenty patients with neuroblastoma who undertook pretreatment FDG PET/CT at our institute between 2008 and 2015 and showed MIBG avidity were retrospectively enrolled in the present study. Clinical information—including histopathology, and serum markers—and several PET parameters—including SUVmax of the primary lesion (Psuv), target-to-background ratio (TBR), metabolic tumor volume (MTV), and coefficient of variation (CV)—were analyzed. The prognostic effect of PET parameters was evaluated in terms of progression-free survival (PFS).RESULTS: Total 20 patients (4.5 ± 3.5 years) were divided as two groups by disease progression. Six patients (30.0 %) experienced disease progression and one patient (5.0 %) died during follow-up period. There were not statistically significant in age, stage, MYCN status, primary tumor size, serum lactate dehydrogenase (LDH), neuron-specific enolase (NSE), and ferritin level between two groups with progression or no progression. However, Psuv (p = 0.017), TBR (p = 0.09), MTV (p = 0.02), and CV (p = 0.036) showed significant differences between two groups. In univariate analysis, PFS was significantly associated with Psuv (p = 0.021) and TBR (p = 0.023).CONCLUSIONS: FDG-PET parameters were significantly related with progression of neuroblastoma. FDG-PET/CT may have the potential as a valuable modality for evaluating prognosis in the patients with MIBG-avid pediatric neuroblastoma.

Pheochromocytoma Developed in a Boy with Multiple Endocrine Neoplasia Type 2A Confirmed by the RET Proto-Oncogene Mutation / 임상소아혈액종양

A 9-year-old boy presented with increased sweating and abdominal pain. His mother and uncle had been diagnosed with bilateral pheochromocytoma and medullary thyroid carcinoma. Magnetic resonance imaging of the boy's abdomen revealed a 7.5 cm×7.0 cm×6.0 cm mass with a thick peripheral enhancing wall and fluid-fluid level at the right suprarenal region. His ¹²³I-meta-iodobenzylguanidine (MIBG) scan showed a large mass with increased MIBG uptake in the right adrenal gland. The levels of serum norepinephrine, urine epinephrine/norepinephrine, metanephrine, and vanillylmandelic acid were elevated. He, his mother, and two sisters tested positive for the known mutation of multiple endocrine neoplasia type 2A, Cys634Tyr in RET proto-oncogene. Laparoscopic tumor excision and right adrenalectomy were performed. Final diagnosis was pheochromocytoma with malignant behavior, based on adrenal gland scoring scale. However, there was no overt metastasis. After surgery, his symptoms resolved and abnormal laboratory tests were normalized.

Pheochromocytoma Developed in a Boy with Multiple Endocrine Neoplasia Type 2A Confirmed by the RET Proto-Oncogene Mutation / 임상소아혈액종양

A 9-year-old boy presented with increased sweating and abdominal pain. His mother and uncle had been diagnosed with bilateral pheochromocytoma and medullary thyroid carcinoma. Magnetic resonance imaging of the boy's abdomen revealed a 7.5 cm×7.0 cm×6.0 cm mass with a thick peripheral enhancing wall and fluid-fluid level at the right suprarenal region. His ¹²³I-meta-iodobenzylguanidine (MIBG) scan showed a large mass with increased MIBG uptake in the right adrenal gland. The levels of serum norepinephrine, urine epinephrine/norepinephrine, metanephrine, and vanillylmandelic acid were elevated. He, his mother, and two sisters tested positive for the known mutation of multiple endocrine neoplasia type 2A, Cys634Tyr in RET proto-oncogene. Laparoscopic tumor excision and right adrenalectomy were performed. Final diagnosis was pheochromocytoma with malignant behavior, based on adrenal gland scoring scale. However, there was no overt metastasis. After surgery, his symptoms resolved and abnormal laboratory tests were normalized.

Elevated Heart Rate is Associated with Cardiac Denervation in Patients with Heart Failure: A 123-Iodine-MIBG Myocardial Scintigraphy Study / Frequência Cardíaca Elevada está Associada com Desnervação Cardíaca em Pacientes com Insuficiência Cardíaca: Um Estudo com Cintilografia Miocárdica com 123-Iodo-MIBG

Abstract Background: In the Systolic Heart Failure Treatment With the If Inhibitor Ivabradine Trial (SHIFT), heart rate (HR) reduction with ivabradine was associated with improved survival and reduced hospitalizations in patients with heart failure (HF). The mechanisms by which elevated HR increases mortality are not fully understood. Objective: To assess the relationship of baseline HR with clinical, neurohormonal and cardiac sympathetic activity in patients with chronic HF and elevated HR. Method: Patients with chronic HF who were in sinus rhythm and had resting HR>70 bpm despite optimal medical treatment were included in a randomized, double-blind study comparing ivabradine versus pyridostigmine. This report refers to the baseline data of 16 initial patients. Baseline HR (before randomization to one of the drugs) was assessed, and patients were classified into two groups, with HR below or above mean values. Cardiac sympathetic activity was assessed by 123-iodine-metaiodobenzylguanidine myocardial scintigraphy. Results: Mean HR was 83.5±11.5 bpm (range 72 to 104), and seven (43.7%) patients had HR above the mean. These patients had lower 6-min walk distance (292.3±93 vs 465.2±97.1 m, p=0.0029), higher values of N-Terminal-proBNP (median 708.4 vs 76.1, p=0.035) and lower late heart/mediastinum rate, indicating cardiac denervation (1.48±0.12 vs 1.74±0.09, p<0.001). Conclusion: Elevated resting HR in patients with HF under optimal medical treatment was associated with cardiac denervation, worse functional capacity, and neurohormonal activation.

Resumo Fundamento: No SHIFT (Systolic Heart Failure Treatment With the If Inhibitor Ivabradine Trial, ou Estudo do Tratamento da Insuficiência Cardíaca Sistólica com o Inibidor de If Ivabradina), a redução da frequência cardíaca (FC) com ivabradina associou-se com melhor sobrevida e redução das hospitalizações em pacientes com insuficiência cardíaca (IC). Os mecanismos pelos quais a FC elevada aumenta a mortalidade não são totalmente compreendidos. Objetivo: Avaliar a relação da FC basal com atividade clínica, neuro-hormonal e simpática cardíaca em pacientes com IC crônica e FC elevada. Método: Pacientes com IC crônica em ritmo sinusal e FC≥70 apesar de tratamento adequado foram incluídos em um estudo duplo-cego, randomizado, que comparou ivabradina com piridostigmina. Este artigo refere-se a dados basais dos primeiros 16 pacientes. A FC basal (antes da randomização para um dos medicamentos) foi avaliada, e os pacientes classificados em dois grupos, com FC abaixo ou acima dos valores médios. A atividade simpática cardíaca foi avaliada por cintilografia com metaiodobenzilguanidina marcada com iodo 123. Resultados: A FC média foi 83,5±11,5 bpm (intervalo 72 a 104), e sete pacientes (43.7%) tinham FC acima da média. Esses pacientes apresentaram menor distância percorrida no teste de caminhada de 6 minutos (292,3±93 vs 465,2±97,1 m, p=0,0029), valores mais altos de N-terminal do pró-BNP (mediana 708,4 vs 76,1, p=0,035) e menor relação coração/mediastino tardia, indicando desnervação cardíaca (1,48±0,12 vs 1,74±0,09, p<0,001). Conclusão: A FC de repouso elevada em pacientes com IC em tratamento médico adequado associou-se com desnervação cardíaca, pior capacidade funcional e ativação neuro-hormonal.

Effect of Nebivolol on MIBG Parameters and Exercise in Heart Failure with Normal Ejection Fraction / Efeito do Nebivolol sobre Parâmetros do MIBG e Exercício na Insuficiência Cardíaca com Fração de Ejeção Normal

Abstract Background: More than 50% of the patients with heart failure have normal ejection fraction (HFNEF). Iodine-123 metaiodobenzylguanidine (123I-MIBG) scintigraphy and cardiopulmonary exercise test (CPET) are prognostic markers in HFNEF. Nebivolol is a beta-blocker with vasodilating properties. Objectives: To evaluate the impact of nebivolol therapy on CPET and123I-MIBG scintigraphic parameters in patients with HFNEF. Methods: Twenty-five patients underwent 123I-MIBG scintigraphy to determine the washout rate and early and late heart-to-mediastinum ratios. During the CPET, we analyzed the systolic blood pressure (SBP) response, heart rate (HR) during effort and recovery (HRR), and oxygen uptake (VO2). After the initial evaluation, we divided our cohort into control and intervention groups. We then started nebivolol and repeated the tests after 3 months. Results: After treatment, the intervention group showed improvement in rest SBP (149 mmHg [143.5-171 mmHg] versus 135 mmHg [125-151 mmHg, p = 0.016]), rest HR (78 bpm [65.5-84 bpm] versus 64.5 bpm [57.5-75.5 bpm, p = 0.028]), peak SBP (235 mmHg [216.5-249 mmHg] versus 198 mmHg [191-220.5 mmHg], p = 0.001), peak HR (124.5 bpm [115-142 bpm] versus 115 bpm [103.7-124 bpm], p= 0.043), HRR on the 1st minute (6.5 bpm [4.75-12.75 bpm] versus 14.5 bpm [6.7-22 bpm], p = 0.025) and HRR on the 2nd minute (15.5 bpm [13-21.75 bpm] versus 23.5 bpm [16-31.7 bpm], p = 0.005), but no change in peak VO2 and 123I-MIBG scintigraphic parameters. Conclusion: Despite a better control in SBP, HR during rest and exercise, and improvement in HRR, nebivolol failed to show a positive effect on peak VO2 and 123I-MIBG scintigraphic parameters. The lack of effect on adrenergic activity may be the cause of the lack of effect on functional capacity.

Resumo Fundamento: Mais de 50% dos pacientes com insuficiência cardíaca têm fração de ejeção preservada (ICFEN). A cintilografia marcada com iodo 123 com metaiodobenzilguanidina (123I-MIBG) e o teste cardiopulmonar do exercício (TCPE) são marcadores de prognóstico da ICFEN. O nebivolol é um betabloqueador com propriedade vasodilatadora. Objetivos: Avaliar o impacto da terapia com nebivolol sobre as variáveis da cintilografia com 123I-MIBG e do TCPE em pacientes com ICFEN. Métodos: Vinte e cinco pacientes realizaram cintilografia com 123I-MIBG para avaliar a taxa de washout e a relação coração/mediastino precoce e tardia. Durante o TCPE, foi analisado o comportamento da pressão arterial sistólica (PAS), frequência cardíaca (FC) durante o esforço e a recuperação (FCR) e o consumo de oxigênio (VO2). Após avaliação inicial, separamos nossa amostra em grupos controle versus intervenção, iniciamos o nebivolol e repetimos os exames após 3 meses. Resultados: Após o tratamento, o grupo intervenção apresentou melhora na PAS (149 mmHg [143,5-171 mmHg] versus 135 mmHg [125-151 mmHg, p = 0,016]), FC em repouso (78 bpm [65,5-84 bpm] versus 64,5 bpm [57,5-75,5 bpm, p = 0,028]), PAS no pico do esforço (235 mmHg [216,5-249 mmHg] versus 198 mmHg [191-220,5 mmHg], p = 0,001), FC no pico do esforço (124,5 bpm [115-142 bpm] versus 115 bpm [103,7-124 bpm], p = 0,043) e FCR no 1º minuto (6,5 bpm [4,75-12,75 bpm] versus 14,5 bpm [6,7-22 bpm], p = 0,025) e no 2º minuto (15,5 bpm [13-21,75 bpm] versus 23,5 bpm [16-31,7 bpm], p = 0,005), porém não apresentou mudança no VO2 de pico e nos parâmetros da cintilografia com 123I-MIBG. Conclusão: Apesar de um melhor controle da PAS e na FC em repouso e durante o esforço e uma melhora na FCR, o nebivolol não ocasionou efeito positivo sobre o VO2 de pico e nos parâmetros da cintilografia com 123I-MIBG. A ausência de efeito sobre a atividade adrenérgica pode ser a causa da falta de efeito sobre a capacidade funcional.

¹²³I-Meta-iodobenzylguanidine Sympathetic Imaging: Standardization and Application to Neurological Diseases / 전남의대학술지

¹²³I-meta-iodobenzylguanidine (MIBG) has become widely applied in Japan since its introduction to clinical cardiology and neurology practice in the 1990s. Neurological studies found decreased cardiac uptake of ¹²³I-MIBG in Lewy-body diseases including Parkinson's disease and dementia with Lewy bodies. Thus, cardiac MIBG uptake is now considered a biomarker of Lewy body diseases. Although scintigraphic images of ¹²³I-MIBG can be visually interpreted, an average count ratio of heart-to-mediastinum (H/M) has commonly served as a semi-quantitative marker of sympathetic activity. Since H/M ratios significantly vary according to acquisition and processing conditions, quality control should be appropriate, and quantitation should be standardized. The threshold H/M ratio for differentiating Lewy-body disease is 2.0-2.1, and was based on standardized H/M ratios to comparable values of medium-energy collimators. Parkinson's disease can be separated from various types of parkinsonian syndromes using cardiac ¹²³I-MIBG, whereas activity is decreased on images of Lewy-body diseases using both ¹²³I-ioflupane for the striatum and ¹²³I-MIBG. Despite being a simple index, the H/M ratio of ¹²³I-MIBG uptake is reproducible and can serve as an effective tool to support a diagnosis of Lewy-body diseases in neurological practice.

¹²³I-Meta-iodobenzylguanidine Sympathetic Imaging: Standardization and Application to Neurological Diseases / 전남의대학술지

¹²³I-meta-iodobenzylguanidine (MIBG) has become widely applied in Japan since its introduction to clinical cardiology and neurology practice in the 1990s. Neurological studies found decreased cardiac uptake of ¹²³I-MIBG in Lewy-body diseases including Parkinson's disease and dementia with Lewy bodies. Thus, cardiac MIBG uptake is now considered a biomarker of Lewy body diseases. Although scintigraphic images of ¹²³I-MIBG can be visually interpreted, an average count ratio of heart-to-mediastinum (H/M) has commonly served as a semi-quantitative marker of sympathetic activity. Since H/M ratios significantly vary according to acquisition and processing conditions, quality control should be appropriate, and quantitation should be standardized. The threshold H/M ratio for differentiating Lewy-body disease is 2.0-2.1, and was based on standardized H/M ratios to comparable values of medium-energy collimators. Parkinson's disease can be separated from various types of parkinsonian syndromes using cardiac ¹²³I-MIBG, whereas activity is decreased on images of Lewy-body diseases using both ¹²³I-ioflupane for the striatum and ¹²³I-MIBG. Despite being a simple index, the H/M ratio of ¹²³I-MIBG uptake is reproducible and can serve as an effective tool to support a diagnosis of Lewy-body diseases in neurological practice.

Paraganglioma Presenting as Dilated Cardiomyopathy with Cardiogenic Shock and Sepsis / 대한내과학회지

Rarely, a paraganglioma can lead to disastrous cardiac complications such as heart failure, cardiomyopathy, or myocardial infarction and inflammatory complications such as sepsis. We describe a 41-year-old man who developed severe dilated cardiomyopathy with cardiogenic shock and sepsis who had a paraganglioma in the retroperitoneum. Echocardiography showed extensive global hypokinesia with severe left ventricular systolic dysfunction. In addition, leukocytosis with elevated inflammatory markers and positive blood cultures indicated sepsis. Abdominal enhanced computed tomography and magnetic resonance imaging showed a large heterogeneous mass with cystic changes in the retroperitoneum. Serum and urine samples indicated elevated levels of catecholamine and its metabolites, and a 131I-meta-iodobenzylguanidine (MIBG) scan indicated uptake of MIBG. After intensive medical treatment and surgical removal of the paraganglioma, the dilated cardiomyopathy and sepsis resolved. The diagnosis of paraganglioma should be considered in patients presenting with acute heart failure or sepsis of nonspecific origin.

Cardioprotective Effect of Fimasartan, a New Angiotensin Receptor Blocker, in a Porcine Model of Acute Myocardial Infarction

Cardioprotective effect of fimasartan, a new angiotensin receptor blocker (ARB), was evaluated in a porcine model of acute myocardial infarction (MI). Fifty swine were randomized to group 1 (sham, n=10), group 2 (no angiotensin-converting enzyme inhibitor [ACEI] or ARB, n=10), group 3 (perindopril 2 mg daily, n=10), group 4 (valsartan 40 mg daily, n=10), or group 5 (fimasartan 30 mg daily, n=10). Acute MI was induced by occlusion of the left anterior descending artery for 50 min. Echocardiography, single photon emission computed tomography (SPECT), and F-18 fluorodeoxyglucose cardiac positron emission tomography (PET) were performed at baseline, 1 week, and 4 weeks. Iodine-123 meta-iodobenzylguanidine (MIBG) scan was done at 6 weeks for visualization of cardiac sympathetic activity. Left ventricular function and volumes at 4 weeks were similar between the 5 groups. No difference was observed in groups 2 to 5 in SPECT perfusion defect, matched and mismatched segments between SPECT and PET at 1 week and 4 weeks. MIBG scan showed similar uptake between the 5 groups. Pathologic analysis showed similar infarct size in groups 2 to 5. Infarct size reduction was not observed with use of fimasartan as well as other ACEI and ARB in a porcine model of acute MI.

The first MIBG therapy in the Philippines

Neuroblastoma is an embryonal tumor of children that frequently presents with metastases. Our patient is a 6-year-old girl who was diagnosed to have neuroblastoma with diffuse metastatic disease throughout the skeleton as seen in her 123I-MIBG scan in the United States. 18F-FDG PET/CT scan was done in the Philippines after chemotherapy and gene therapy, and before 131I-MIBG therapy. No additional lesions were seen on PET.  131I-MIBG was then performed and an 131I-MIBG with SPECT/CT thereafter, which showed an increase in size and extent of the lesion in the head and a decrease in number of the skeletal metastases. New 131I-MIBG-avid posterior cervical lymph nodes were also localized through SPECT/CT. For this patient, a follow-up 123I/131I-MIBG scan would be more cost-effective in assessing response to therapy. Sectional imaging may be done to obviate the need for sedation of this young patient.

Clinical experience with 18F-fluorodeoxyglucose positron emission tomography and 123I-metaiodobenzylguanine scintigraphy in pediatric neuroblastoma: complementary roles in follow-up of patients / 소아과

PURPOSE: To evaluate the potential utility of 123I-metaiodobenzylguanine (123I-MIBG) scintigraphy and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) for the detection of primary and metastatic lesions in pediatric neuroblastoma (NBL) patients, and to determine whether 18F-FDG PET is as beneficial as 123I-MIBG imaging. METHODS: We selected 8 NBL patients with significant residual mass after operation and who had paired 123I-MIBG and 18F-FDG PET images that were obtained during the follow-up. We retrospectively reviewed the clinical charts and the findings of 45 paired scans. RESULTS: Both scans correlated relatively well with the disease status as determined by standard imaging modalities during follow-up; the overall concordance rates were 32/45 (71.1%) for primary tumor sites and 33/45 (73.3%) for bone-bone marrow (BM) metastatic sites. In detecting primary tumor sites, 123I-MIBG might be superior to 18F-FDG PET. The sensitivity of 123I-MIBG and 18F-FDG PET were 96.7% and 70.9%, respectively, and their specificity were 85.7% and 92.8%, respectively. 18F-FDG PET failed to detect 9 true NBL lesions in 45 follow-up scans (false negative rate, 29%) with positive 123I-MIBG. For bone-BM metastatic sites, the sensitivity of 123I-MIBG and 18F-FDG PET were 72.7% and 81.8%, respectively, and the specificity were 79.1% and 100%, respectively. 123I-MIBG scan showed higher false positivity (20.8%) than 18F-FDG PET (0%). CONCLUSION: 123I-MIBG is superior for delineating primary tumor sites, and 18F-FDG PET could aid in discriminating inconclusive findings on bony metastatic NBL. Both scans can be complementarily used to clearly determine discrepancies or inconclusive findings on primary or bone-BM metastatic NBL during follow-up.