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BACKGROUND: Isolated rapid eye movement sleep behavior disorder (iRBD) serves as a prodromal phase of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Blunted tachycardia (BT) during postural changes indicates neurogenic orthostatic hypotension, a marker of autonomic dysfunction. We aimed to investigate whether BT is associated with cardiac sympathetic neurogenic denervation. Additionally, we conducted a preliminary short-term follow-up to examine the potential prognostic significance of BT regarding phenoconversion and mortality. METHODS: Forty-three patients with iRBD at Shiga University of Medical Science Hospital underwent active standing tests to identify BT, defined by a specific ratio of decrease in systolic blood pressure to inadequate increase in heart rate after standing, and orthostatic hypotension. 123I-metaiodobenzylguanidine myocardial scintigraphy (123I-MIBG) and dopamine transporter single-photon emission computed tomography (DAT-SPECT) were performed. Participants were followed up for 3.4 ± 2.4 years for phenoconversion and 4.0 ± 2.3 years for mortality assessment, and the risk of events was analyzed using log-rank tests. RESULTS: Among the 43 participants (mean age, 72.3 ± 7.9 years; 8 female), 17 met the BT criteria. We found no significant comorbidity-related differences in hypertension or diabetes between the BT(+) and BT(-) groups. Orthostatic hypotension was more prevalent in the BT(+) group than in the BT(-) group (47.1% vs 7.7%, p = 0.003). BT(+) patients were older with a lower early and delayed MIBG uptake; however, no significant differences were observed in DAT accumulation. Phenoconversion was observed in seven (41.2%) BT(+) and seven (26.9%) BT(-) patients. Three deaths were recorded in the BT(+) group (17.6%) and three in the BT(-) group (11.5%). No significant differences were observed in the risk of phenoconversion or mortality between the groups. CONCLUSIONS: We have identified the possibility that BT reflects cardiac sympathetic neurogenic denervation in patients with iRBD. Future research is needed to elucidate the potential prognostic value of BT.
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Trastorno de la Conducta del Sueño REM , Taquicardia , Humanos , Masculino , Femenino , Anciano , Trastorno de la Conducta del Sueño REM/diagnóstico , Taquicardia/diagnóstico , Corazón/inervación , Persona de Mediana Edad , Tomografía Computarizada de Emisión de Fotón Único/métodos , Anciano de 80 o más Años , Simpatectomía/métodos , 3-Yodobencilguanidina , Estudios de SeguimientoRESUMEN
BACKGROUND: In contrast to the well-known prognostic values of the cardiorenal linkage, it remains unclear whether impaired cognitive function affects cardiac prognosis in relation to cardiac sympathetic innervation and renal function in patients with heart failure (HF). METHODS AND RESULTS: A total of 433 consecutive HF patients with left ventricular ejection fraction (LVEF) <50% underwent the Mini-Mental State Examination (MMSE) and a neuropsychological test for screening of cognition impairment or subclinical dementia. Following metaiodobenzylguanidine (MIBG) scintigraphy, patient outcomes with a primary endpoint of lethal cardiac events (CEs) were evaluated for a mean period of 14.8 months. CEs were documented in 84 HF patients during follow-up. MMSE score, estimated glomerular filtration rate (eGFR) and standardized heart-to-mediastinum ratio of MIBG activity (sHMR) were significantly reduced in patients with CEs compared with patients without CEs. Furthermore, overall multivariate analysis revealed that these parameters were significant independent determinants of CEs. The cutoff values of MMSE score (<26), sHMR (<1.80) and eGFR (<47.0 mL/min/1.73 m2) determined by receiver operating characteristic (ROC) analysis successfully differentiated HF patients at more increased risk for CEs from other HF patients. CONCLUSIONS: Impairment of cognitive function is not only independently related to but also synergistically increases cardiac mortality risk in association with cardiac sympathetic function and renal function in patients with HF.
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Insuficiencia Cardíaca Sistólica , Simpatectomía , Humanos , Anciano , Masculino , Femenino , Persona de Mediana Edad , Insuficiencia Cardíaca Sistólica/mortalidad , Insuficiencia Cardíaca Sistólica/fisiopatología , Insuficiencia Cardíaca Sistólica/complicaciones , Tasa de Filtración Glomerular , Disfunción Cognitiva/etiología , Disfunción Cognitiva/mortalidad , 3-Yodobencilguanidina , Riñón/fisiopatología , Riñón/inervación , Corazón/inervación , Corazón/fisiopatología , Enfermedades Renales/mortalidad , Enfermedades Renales/fisiopatología , Factores de Riesgo , Cognición , Anciano de 80 o más Años , PronósticoRESUMEN
BACKGROUND: 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. MATERIALS AND METHODS: Retrospective data from 476 patient encounters from the PHIS from 2010 to 2019. RESULTS: Total 240/476 (50.45%) children evaluated were under 6 years 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 0-3 years age group compared to children older than 3 years of age (14.19% vs. 5.80%, p < .001). Opiate was the most used medication in children greater than 3 years compared to the 0-3-year age group (36.23 vs. 23.87, p < .05). CONCLUSION: 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.
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3-Yodobencilguanidina , Bases de Datos Factuales , Unidades de Cuidado Intensivo Pediátrico , Neuroblastoma , Humanos , Preescolar , Lactante , Niño , Masculino , Femenino , Estudios Retrospectivos , Neuroblastoma/radioterapia , 3-Yodobencilguanidina/uso terapéutico , 3-Yodobencilguanidina/administración & dosificación , Adolescente , Recién Nacido , Analgesia/métodos , Analgesia/estadística & datos numéricos , Radioisótopos de Yodo/uso terapéutico , Radioisótopos de Yodo/administración & dosificación , Hipnóticos y Sedantes/administración & dosificación , Hipnóticos y Sedantes/uso terapéutico , Estudios de Seguimiento , Pronóstico , Radiofármacos/uso terapéutico , Radiofármacos/administración & dosificaciónRESUMEN
Pheochromocytomas are rare tumours originating in chromafï¬n cells, representing 0.1%-1% of all secondary hypertension cases. The majority are benign and unilateral, characterised by the production of catecholamines and other neuropeptides. Mainly located in the adrenal gland, they are more frequent between the third and fifth decades of life. Iodine-131 metaiodobenzylguanidine (131I-MIBG), a radiopharmaceutical agent used for scintigraphic localisation of pheochromocytomas, has been employed to treat malignant pheochromocytomas since 1983 in a few specialised centres around the world. We reviewed our clinical experience in one such case of a young lady who presented with history of abdominal pain, headache and lower back pain. On evaluation, ultrasonography revealed a right adrenal mass and elevated urine vanillylmandelic acid levels. Following surgical resection and histopathological confirmation of pheochromocytoma, MIBG scintigraphy revealed osseous metastases and hence, she underwent 131I-MIBG therapy.
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3-Yodobencilguanidina , Neoplasias de las Glándulas Suprarrenales , Feocromocitoma , Radiofármacos , Humanos , 3-Yodobencilguanidina/uso terapéutico , Femenino , Neoplasias de las Glándulas Suprarrenales/secundario , Radiofármacos/uso terapéutico , Adulto , Supervivencia sin Enfermedad , Radioisótopos de Yodo/uso terapéutico , Neoplasias Óseas/secundario , Neoplasias Óseas/radioterapia , CintigrafíaRESUMEN
BACKGROUND: Tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) and incorporation of 131I-metaiodobenzylguanidine (131I-MIBG) treatment have shown positive outcomes in high-risk neuroblastoma. However, more optimized treatment strategies are still needed. PROCEDURE: The NB-2014 study was a nonrandomized, prospective trial that examined survival outcomes in metastatic high-risk neuroblastoma patients using response-adapted consolidation therapy. We used post-induction residual 123I-MIBG status at metastatic sites as a treatment response marker. Patients achieving complete resolution of MIBG uptake at metastatic sites underwent a reduced first HDCT/auto-SCT with a 20% dose reduction in HDCT. After the first HDCT/auto-SCT, patients with remaining MIBG uptake received dose-escalated (18 mCi/kg) 131I-MIBG treatment. In contrast, those with complete resolution of MIBG at metastatic sites received a standard dose (12 mCi/kg) of 131I-MIBG. We compared survival and toxicity outcomes with a historical control group from the NB-2009. RESULTS: Of 65 patients treated, 63% achieved complete resolution of MIBG uptake at metastatic sites following induction chemotherapy, while 29% of patients still had MIBG uptake at metastatic sites after the first HDCT/auto-SCT. The 3-year event-free survival (EFS) and overall survival (OS) rates were 68.2% ± 6.0% and 86.5% ± 4.5%, respectively. Compared to NB-2009, EFS was similar (p = .855); however, NB-2014 had a higher OS (p = .031), a lower cumulative incidence of treatment-related mortality (p = .036), and fewer acute and late toxicities. CONCLUSIONS: Our results suggest that response-adaptive consolidation therapy based on chemotherapy response at metastatic sites facilitates better treatment tailoring, and appears promising for patients with metastatic high-risk neuroblastoma.
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3-Yodobencilguanidina , Quimioterapia de Consolidación , Neuroblastoma , Humanos , Neuroblastoma/terapia , Neuroblastoma/mortalidad , Neuroblastoma/patología , Neuroblastoma/tratamiento farmacológico , Femenino , Masculino , Preescolar , Lactante , Niño , 3-Yodobencilguanidina/uso terapéutico , Estudios Prospectivos , Tasa de Supervivencia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Adolescente , Estudios de Seguimiento , Trasplante Autólogo , Pronóstico , Trasplante de Células Madre Hematopoyéticas , RadiofármacosRESUMEN
Meta-[123I]iodobenzylguanidine ([123I]MIBG) scintigraphy with SPECT/CT is the standard of care for diagnosing and monitoring neuroblastoma. Replacing [123I]MIBG with the new PET tracer meta-[18F]fluorobenzylguanidine ([18F]MFBG) and further improving sensitivity and reducing noise in a new long-axial-field-of-view (LAFOV) PET/CT scanner enable increased image quality and a faster acquisition time, allowing examinations to be performed without sedation or general anesthesia (GA). Focusing on feasibility, we present our first experience with [18F]MFBG LAFOV PET/CT and compare it with [123I]MIBG scintigraphy plus SPECT/CT for imaging in neuroblastoma in children. Methods: A pilot of our prospective, single-center study recruited children with neuroblastoma who were referred for [123I]MIBG scintigraphy with SPECT/CT. Within 1 wk of [123I]MIBG scintigraphy and SPECT/low-dose CT, [18F]MFBG LAFOV PET/ultra-low-dose CT was performed 1 h after injection (1.5-3 MBq/kg) without sedation or GA, in contrast to the 24-h postinjection interval needed for scanning with [123I]MIBG, the 2- to 2.5-h acquisition time, and the GA often needed in children less than 6 y old. Based on the spirocyclic iodonium-ylide precursor, [18F]MFBG was produced in a fully automated good manufacturing practice-compliant procedure. We present the feasibility of the study. Results: In the first paired scans of the first 10 children included (5 at diagnosis, 2 during treatment, 2 during surveillance, and 1 at relapse), [18F]MFBG PET/CT scan showed a higher number of radiotracer-avid lesions in 80% of the cases and an equal number of lesions in 20% of the cases. The SIOPEN score was higher in 50% of the cases, and the Curie score was higher in 70% of the cases. In particular, intraspinal, retroperitoneal lymph node, and bone marrow involvement was diagnosed with much higher precision. None of the children (median age, 1.6 y; range, 0.1-7.9 y) had sedation or GA during the PET procedure, whereas 80% had GA during [123I]MIBG scintigraphy with SPECT/CT. A PET acquisition time of only 2 min without motion artifacts was the data requirement of the 10-min acquisition time for reconstruction to provide a clinically useful image. Conclusion: This pilot study demonstrates the feasibility of performing [18F]MFBG LAFOV PET/CT for imaging of neuroblastoma. Further, an increased number of radiotracer-avid lesions, an increased SIOPEN score, and an increased Curie score were seen on [18F]MFBG LAFOV PET/CT compared with [123I]MIBG scintigraphy with SPECT/CT, and GA and sedation was avoided in all patients. Thus, with a 1-d protocol, a significantly shorter scan time, a higher sensitivity, and the avoidance of GA and sedation, [18F]MFBG LAFOV PET/CT shows promise for future staging and response assessment and may also have a clinical impact on therapeutic decision-making for children with neuroblastoma.
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Anestesia General , Neuroblastoma , Tomografía Computarizada por Tomografía de Emisión de Positrones , Neuroblastoma/diagnóstico por imagen , Humanos , Preescolar , Femenino , Masculino , Niño , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Lactante , 3-Yodobencilguanidina , Guanidinas , Estudios Prospectivos , Proyectos Piloto , RadiofármacosRESUMEN
BACKGROUND: 123Iodine-meta-iodobenzylguanidine scintigraphy is useful for assessing cardiac autonomic dysfunction and predict outcomes in heart failure (HF). The relationship of cardiac sympathetic function with myocardial remodeling and diffuse fibrosis remains largely unknown. We aimed to evaluate the cardiac sympathetic function of patients with HF and its relation with myocardial remodeling and exercise capacity. METHODS AND RESULTS: Prospectively enrolled patients with HF (New York Heart Association class II-III) were stratified into HF with preserved left ventricular ejection fraction [LVEF] ≥45%) and reduced LVEF. Ventricular morphology/function and myocardial extracellular volume (ECV) fraction were quantified by cardiovascular magnetic resonance, global longitudinal strain by echocardiography, cardiac sympathetic function by heart-to-mediastinum ratio from 123iodine-meta-iodobenzylguanidine scintigraphy. All participants underwent cardiopulmonary exercise testing. The cohort included 33 patients with HF with preserved LVEF (LVEF, 60±10%; NT-proBNP [N-terminal pro-B-type natriuretic peptide], 248 [interquartile range, 79-574] pg/dL), 28 with HF with reduced LVEF (LVEF, 30±9%; NT-proBNP, 743 [interquartile range, 250-2054] pg/dL) and 20 controls (LVEF, 65±5%; NT-proBNP, 40 [interquartile range, 19-50] pg/dL). Delayed (4 hours) 123iodine-meta-iodobenzylguanidine heart-to-mediastinum ratio was lower in HF with preserved LVEF (1.59±0.25) and HF with reduced LVEF (1.45±0.16) versus controls (1.92±0.24; P<0.001), and correlated negatively with diffuse fibrosis assessed by ECV (R=-0.34, P<0.01). ECV in segments without LGE was increased in HF with preserved ejection fraction (0.32±0.05%) and HF with reduced left ventricular ejection fraction (0.31±0.04%) versus controls (0.28±0.04, P<0.05) and was associated with the age- and sex-adjusted maximum oxygen consumption (peak oxygen consumption); (R=-0.41, P<0.01). Preliminary analysis indicates that cardiac sympathetic function might potentially act as a mediator in the association between ECV and NT-proBNP levels. CONCLUSIONS: Abnormally low cardiac sympathetic function in patients with HF with reduced and preserved LVEF is associated with extracellular volume expansion and decreased cardiopulmonary functional capacity.
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Biomarcadores , Insuficiencia Cardíaca , Volumen Sistólico , Sistema Nervioso Simpático , Remodelación Ventricular , Humanos , Masculino , Femenino , Insuficiencia Cardíaca/fisiopatología , Persona de Mediana Edad , Remodelación Ventricular/fisiología , Sistema Nervioso Simpático/fisiopatología , Anciano , Biomarcadores/sangre , Volumen Sistólico/fisiología , Estudios Prospectivos , Función Ventricular Izquierda/fisiología , Fragmentos de Péptidos/sangre , Péptido Natriurético Encefálico/sangre , Tolerancia al Ejercicio/fisiología , Fibrosis , 3-Yodobencilguanidina , Prueba de Esfuerzo , Miocardio/patología , Miocardio/metabolismo , Corazón/inervación , Corazón/fisiopatología , Ecocardiografía , Radiofármacos , CintigrafíaRESUMEN
Background: Dementia with Lewy bodies (DLB) presents with various symptoms, posing challenges for early diagnosis challenging. Dopamine transporter (123I-FP-CIT) single-photon emission tomography (SPECT) and 123I-meta-iodobenzylguanidine (123I-MIBG) imaging are crucial diagnostic biomarkers. Hypothesis about body- and brain-first subtypes of DLB indicate that some DLB may show normal 123I-FP-CIT or 123I-MIBG results; but the characteristic expression of these two subtypes remains unclear. Objective: This study aimed to evaluate the diagnostic sensitivity of 123I-FP-CIT and 123I-MIBG imaging alone, combined in patients with DLB and explore symptoms associated with the abnormal imaging results. Methods: Demographic data, clinical status, and imaging results were retrospectively collected from patients diagnosed with possible DLB. Both images were quantified using semi-automated software, and the sensitivity of each imaging modality and their combination was calculated. Demographic data, cognition, and motor and non-motor symptoms were compared among the subgroups based on the imaging results. Symptoms related to each imaging abnormality were examined using binomial logistic regression analyses. Results: Among 114 patients with DLB, 80 underwent 123I-FP-CIT SPECT (sensitivity: 80.3%), 83 underwent 123I-MIBG imaging (68.2%), and 66 both (sensitivity of either abnormal result: 93.9%). Visual hallucinations differed among the four subgroups based on imaging results. Additionally, nocturia and orthostatic hypotension differed between abnormal and normal 123I-MIBG images. Conclusions: Overall, 123I-FP-CIT SPECT was slightly higher sensitivity than 123I-MIBG imaging, with combined imaging increasing diagnostic sensitivity. Normal results of a single imaging test may not refute DLB. Autonomic symptoms may lead to abnormal 123I-MIBG scintigraphy findings indicating body-first subtype of patients with DLB.
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3-Yodobencilguanidina , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática , Enfermedad por Cuerpos de Lewy , Tomografía Computarizada de Emisión de Fotón Único , Tropanos , Humanos , Enfermedad por Cuerpos de Lewy/diagnóstico por imagen , Enfermedad por Cuerpos de Lewy/metabolismo , Masculino , Femenino , Anciano , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Estudios Retrospectivos , Anciano de 80 o más Años , Sensibilidad y Especificidad , Radiofármacos , Imagen de Perfusión Miocárdica , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Persona de Mediana Edad , Imágenes DopaminérgicasRESUMEN
ABSTRACT: A 17-year-old boy with Von Hippel-Lindau syndrome presented with hypertension, raised plasma catecholamines, and MRI findings of a new pancreatic tail lesion and 2 stable right adrenal lesions concerning for functional neuroendocrine tumors. A 68 Ga-DOTATATE PET/CT demonstrated intense tracer avidity within the pancreatic lesion with minimal uptake in the adrenal lesions. Conversely, a 123 I-MIBG SPECT/CT study demonstrated high-grade tracer uptake within the adrenal lesions, with no significant uptake appreciated in the pancreatic lesion. The adrenal lesions were resected, and pathology was consistent with pheochromocytoma. Plasma catecholamines returned to within the normal range and hypertension resolved.
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3-Yodobencilguanidina , Neoplasias de las Glándulas Suprarrenales , Compuestos Organometálicos , Feocromocitoma , Tomografía Computarizada por Tomografía de Emisión de Positrones , Tomografía Computarizada por Tomografía Computarizada de Emisión de Fotón Único , Enfermedad de von Hippel-Lindau , Humanos , Feocromocitoma/diagnóstico por imagen , Adolescente , Masculino , Enfermedad de von Hippel-Lindau/diagnóstico por imagen , Enfermedad de von Hippel-Lindau/complicaciones , Neoplasias de las Glándulas Suprarrenales/diagnóstico por imagenRESUMEN
OBJECTIVE: We aimed to establish a practical diagnostic index for Lewy body diseases (LBD), such as Parkinson's disease and dementia, with Lewy bodies in outpatient settings and criteria for exempting patients from late imaging. METHODS: We acquired early and late 123I-metaiodobenzylguanidine (MIBG) images from 108 consecutive patients with suspected LBD and standardized heart-to-mediastinum (H/M) ratios for collimator conditions. Exclusions included young-onset Parkinson's disease (age < 50 years) and genetic transthyretin-type amyloidosis. We developed logistic models incorporating H/M ratios with or without age (n = 92). The sympathetic MIBG index for LBD (SMILe index), categorized LBD likelihood from 0 (lowest) to 1 (highest). Diagnostic accuracy was assessed as the area under the receiver operating characteristic (ROC) curve (AUC). The characteristics of the new index were compared with H/M ratios. The need for late imaging was explored using the SMILe index. RESULTS: Early or late SMILe indexes using a single H/M ratio variable discriminated LBD from non-LBD. The AUC values for early and late SMILe indexes were 0.880 and 0.894 (p < 0.0001 for both), identical to those for early and late H/M ratios. The sensitivity and the specificity of early SMILe indexes with a 0.5 threshold were 76% and 90%, achieving accuracy of accuracy 86%. Similarly, the late SMILe index demonstrated a sensitivity of 76% and specificity of 87%, with an accuracy of 84%. Early SMILe indexes < 0.3 or > 0.7 (representing 84% patients) indicated a diagnosis without a late MIBG study. CONCLUSION: The 123I-MIBG-derived SMILe indexes provide likelihood of LBD, and those with a 50% threshold demonstrated optimal diagnostic accuracy for LBD. The index values of either < 0.3 or > 0.7 accurately selected patients who do not need late imaging.
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3-Yodobencilguanidina , Enfermedad por Cuerpos de Lewy , Humanos , Enfermedad por Cuerpos de Lewy/diagnóstico por imagen , Masculino , Femenino , Anciano , Persona de Mediana Edad , Anciano de 80 o más Años , Probabilidad , Curva ROC , Factores de Tiempo , Mediastino/diagnóstico por imagenRESUMEN
This study aimed to compare tumor lesion detectability and diagnostic accuracy of whole-body magnetic resonance imaging (WB-MRI) and radioiodine-labeled meta-iodo-benzylguanidine (mIBG) imaging techniques in patients with metastatic pheochromocytoma and paraganglioma (PPGL). This retrospective study included 13 patients had pheochromocytoma and 5 had paraganglioma, who were all suspected of having metastatic tumors. Each patient underwent WB-MRI and 123I-mIBG as a pretreatment screening for 131I-mIBG therapy. Two expert reviewers evaluated WB-MRI, 123I-mIBG images, and post-therapy 131I-mIBG images for the presence of metastatic lesions in the lungs, bones, liver, lymph nodes, and other organs. Diagnostic measures for detecting metastatic lesions, including sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), and receiver operating characteristics (ROC)-area under the curve (AUC), were calculated for each imaging technique. We analyzed WB-MRI images for detecting metastatic lesions, which demonstrated sensitivity, specificity, accuracy, PPV, NPV, and AUC of 82%, 97%, 90%, 96%, 86%, and 0.92, respectively. These values were 83%, 95%, 89%, 94%, 86%, and 0.90 in 123I-mIBG images and 85%, 92%, 89%, 91%, 87%, and 0.91 in post-therapy 131I-mIBG images, respectively. Our results reveal the comparable diagnostic accuracy of WB-MRI to one of the mIBG images.
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3-Yodobencilguanidina , Neoplasias de las Glándulas Suprarrenales , Radioisótopos de Yodo , Imagen por Resonancia Magnética , Paraganglioma , Feocromocitoma , Imagen de Cuerpo Entero , Humanos , Feocromocitoma/diagnóstico por imagen , Feocromocitoma/patología , Paraganglioma/diagnóstico por imagen , Femenino , Masculino , Imagen por Resonancia Magnética/métodos , Persona de Mediana Edad , Adulto , Imagen de Cuerpo Entero/métodos , Neoplasias de las Glándulas Suprarrenales/diagnóstico por imagen , Neoplasias de las Glándulas Suprarrenales/patología , Estudios Retrospectivos , Anciano , Metástasis de la Neoplasia , Radiofármacos , Sensibilidad y Especificidad , Adulto JovenRESUMEN
Heart failure (HF) is a chronic disease affecting 1%-2% of the global population.123I-labeled meta-iodobenzylguanidine (mIBG) is US Food and Drug Administration-approved for cardiac imaging and prognosis risk assessment in patients with HF. As a norepinephrine analog, mIBG is believed to be transported into adrenergic nerve terminals by the neuronal norepinephrine transporter (NET) and hence image sympathetic innervation of the myocardium. We previously showed that mIBG is an excellent substrate of organic cation transporter 3 (OCT3), an extraneuronal transporter expressed in cardiomyocytes. Here, we evaluated the in vivo impact of Oct3 on mIBG disposition and tissue distribution using Oct3 knockout mice. Oct3 +/+ and Oct3 -/- mice were administered with mIBG intravenously, and mIBG plasma pharmacokinetics and tissue exposures were determined. In Oct3 +/+ mice, mIBG exhibited extensive accumulation in multiple tissues (heart, salivary gland, liver, and adrenal gland). No difference was observed in overall plasma exposure between Oct3 +/+ and Oct3 -/- mice. Strikingly, cardiac mIBG was depleted in Oct3 -/- mice, resulting in 83% reduction in overall cardiac exposure (AUC0-24 h: 12.7 vs. 2.1 µg × h/g). mIBG tissue exposure (AUC0-24 h) was also reduced by 66%, 36%, and 31% in skeletal muscle, salivary gland, and lung, respectively, in Oct3 -/- mice. Our data demonstrated that Oct3 is the primary transporter responsible for cardiac mIBG uptake in vivo and suggested that cardiac mIBG imaging mainly measures OCT3 activity in cardiomyocytes but not NET-mediated uptake in adrenergic nerve endings. Our findings challenge the current paradigm in interpreting cardiac mIBG imaging results and suggest OCT3 as a potential genetic risk marker for HF prognosis. SIGNIFICANCE STATEMENT: 123I-labeled meta-iodobenzylguanidine is used for cardiac imaging and risk assessment in heart failure patients. Contrary to the current belief that meta-iodobenzylguanidine (mIBG) tracks cardiac sympathetic innervation due to its uptake by the neuronal norepinephrine transporter, the authors demonstrated that cardiac mIBG uptake is mediated by the extraneuronal transporter Oct3. Their findings warrant a re-evaluation of the scientific rationale behind cardiac mIBG scan and further suggest organic cation transporter 3 as a risk factor for disease progression in heart failure patients.
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3-Yodobencilguanidina , Ratones Noqueados , Miocardio , Factor 3 de Transcripción de Unión a Octámeros , Animales , Ratones , 3-Yodobencilguanidina/farmacocinética , 3-Yodobencilguanidina/metabolismo , Miocardio/metabolismo , Distribución Tisular , Masculino , Factor 3 de Transcripción de Unión a Octámeros/metabolismo , Radiofármacos/farmacocinética , Corazón/diagnóstico por imagen , Corazón/inervación , Ratones Endogámicos C57BL , Insuficiencia Cardíaca/metabolismo , Insuficiencia Cardíaca/diagnóstico por imagen , Proteínas de Transporte de Noradrenalina a través de la Membrana Plasmática/metabolismoAsunto(s)
3-Yodobencilguanidina , Paraganglioma , Radiofármacos , Tomografía Computarizada por Tomografía Computarizada de Emisión de Fotón Único , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/diagnóstico por imagen , Neoplasias de la Vejiga Urinaria/cirugía , Tomografía Computarizada por Tomografía Computarizada de Emisión de Fotón Único/métodos , Paraganglioma/diagnóstico por imagen , Paraganglioma/cirugía , Radioisótopos de Yodo/uso terapéutico , Masculino , Persona de Mediana Edad , FemeninoRESUMEN
This continuing education aims to present in a clear and easy-to-understand manner the biology of paragangliomas and pheochromocytomas (PPGLs), the functional imaging studies available for their diagnosis and therapeutic planning, the requirements necessary to administer radioligand therapy (RLT) and the characteristics of these treatments (inclusion criteria, administration protocols, adverse effects and future perspectives). In this pathology we have two RLT options: [131I]MIBG and [177Lu]Lu-DOTA-TATE. The indication for treatment is determined by the expression of its therapeutic target in functional imaging studies, allowing precision and personalized medicine. Although most of the results we have for both treatments have as origin small retrospective series, RLT is presented as a safe and well-tolerated therapeutic option in PPGLs with slow-moderate progression or with uncontrollable symptoms, obtaining high disease control rates.
Asunto(s)
3-Yodobencilguanidina , Neoplasias de las Glándulas Suprarrenales , Paraganglioma , Feocromocitoma , Radiofármacos , Humanos , Feocromocitoma/radioterapia , Feocromocitoma/diagnóstico por imagen , Neoplasias de las Glándulas Suprarrenales/radioterapia , Neoplasias de las Glándulas Suprarrenales/diagnóstico por imagen , Paraganglioma/radioterapia , Paraganglioma/diagnóstico por imagen , Radiofármacos/uso terapéutico , Radiofármacos/farmacocinética , 3-Yodobencilguanidina/uso terapéutico , Octreótido/análogos & derivados , Octreótido/uso terapéutico , Compuestos Organometálicos/uso terapéutico , Medicina de Precisión , Radioisótopos de Yodo/uso terapéutico , Nanomedicina Teranóstica/métodosRESUMEN
Paragangliomas can metastasize, posing potential challenges both in symptomatic management and disease control. Systemic targeted radiotherapies using 131I-MIBG and 177Lu-DOTATATE are a mainstay in the treatment of metastatic paragangliomas. This clinical scenario and discussion aim to enhance physicians' knowledge of the stepwise approach to treat these patients with paraganglioma-targeted radiotherapies. It comprehensively discusses current approaches to selecting paraganglioma patients for targeted radiotherapies and how to choose between the two radiotherapies based on specific patient and tumor characteristics, when either therapy is feasible, or one is superior to another. The safety, efficacy, toxicity profiles, and optimization of these radiotherapies are also discussed, along with other therapeutic options including radiotherapies, available for patients besides these two therapies. Perspectives in radiotherapies of paraganglioma patients are outlined since they hold promising approaches in the near future that can improve patient outcomes.
Asunto(s)
Paraganglioma , Humanos , Paraganglioma/radioterapia , Paraganglioma/patología , Radiofármacos/uso terapéutico , 3-Yodobencilguanidina/uso terapéutico , Octreótido/análogos & derivados , Octreótido/uso terapéutico , Compuestos Organometálicos/uso terapéutico , Neoplasias de las Glándulas Suprarrenales/radioterapiaRESUMEN
Among clinically used radiopharmaceuticals, iodine-123 labeled metaiodobenzylguanidine ([123I]mIBG) serves for diagnosing neuroendocrine tumors and obtaining images of myocardial sympathetic innervation. mIBG, a structural analogue of norepinephrine (NE), a neurotransmitter acting in peripheral and central nerves, follows a pathway similar to NE, transmitting signals through the NE transporter (NET) located at synaptic terminals. It moves through the body without decomposing, enabling noninvasive image evaluation. In this study, we aimed to quantify [123I]mIBG uptake in the adrenal glands using small animal single-photon emission computed tomography/computed tomography (SPECT/CT) images post [123I]mIBG administration. We investigated the possibility of assessing the effectiveness of ß-adrenergic receptor blockers by quantifying SPECT/CT images and biodistribution results to determine the degree of [123I]mIBG uptake in the adrenal glands treated with labetalol, a known ß-adrenergic receptor blocker. Upon intravenous administration of [123I]mIBG to mice, SPECT/CT images were acquired over time to confirm the in vivo distribution pattern, revealing a clear uptake in the adrenal glands. Labetalol inhibited the uptake of [123I]mIBG in cell lines expressing NET. A decrease in [123I]mIBG uptake in the adrenal glands was observed in the labetalol-treated group compared with the normal group through SPECT/CT imaging and biodistribution studies. These results demonstrate that SPECT/CT imaging with [123I]mIBG could be applicable for evaluating the preclinical efficacy of new antihypertensive drug candidates such as labetalol, a ß-adrenergic receptor blocker.
Asunto(s)
3-Yodobencilguanidina , Antagonistas Adrenérgicos beta , Radioisótopos de Yodo , Labetalol , Animales , Humanos , Masculino , Ratones , Glándulas Suprarrenales/diagnóstico por imagen , Glándulas Suprarrenales/efectos de los fármacos , Glándulas Suprarrenales/metabolismo , Antagonistas Adrenérgicos beta/farmacología , Antagonistas Adrenérgicos beta/farmacocinética , Línea Celular Tumoral , Estudios de Factibilidad , Proteínas de Transporte de Noradrenalina a través de la Membrana Plasmática/metabolismo , Proteínas de Transporte de Noradrenalina a través de la Membrana Plasmática/antagonistas & inhibidores , Radiofármacos/farmacocinética , Tomografía Computarizada por Tomografía Computarizada de Emisión de Fotón Único , Distribución TisularRESUMEN
PATIENTS AND METHODS: The primary endpoints were objective response rate (ORR) and disease control rate (DCR). Secondary endpoints were duration of response, blood pressure control, safety, overall and progression-free survival rates, MIBG uptake, and correlations with genetic background. RESULTS: The study included 25 patients. Twenty-four patients had distant metastases, 17 (68%) had hormonally active tumors, and 13 (52%) had previously received antineoplastic treatment. In 24 evaluable patients, the ORR was 38%, including 2 patients with complete response, and the DCR was 83%; median time to response was 12.5 months (95% confidence interval, 4.6-25.1). Twelve patients had sporadic disease, among whom the ORR was 25% and DCR was 83%. Twelve patients had hereditary disease ( SDHB , VHL , RET ); among these, the ORR was 50%, and DCR was 83%. Plasma metanephrines normalized in 30% of patients and improved by greater than 50% in 46%. Sixteen patients had hormonally active tumors and hypertension; in 9 (56%) of these, blood pressure normalized, leading to discontinuation of antihypertensive therapy.The most common adverse events were grades 1-2 nausea/vomiting and transient bone marrow suppression. One patient developed premature ovarian failure. Reversible grades 3-4 myelosuppression were seen in 7 patients (28%). One patient had fatal pneumonitis. CONCLUSIONS: HSA- 131 I-MIBG is associated with a high DCR in patients with MPPGL, regardless of underlying genetic mutation.
Asunto(s)
3-Yodobencilguanidina , Neoplasias de las Glándulas Suprarrenales , Paraganglioma , Feocromocitoma , Humanos , Feocromocitoma/diagnóstico por imagen , Feocromocitoma/radioterapia , Feocromocitoma/tratamiento farmacológico , Femenino , Masculino , Paraganglioma/radioterapia , Paraganglioma/diagnóstico por imagen , Paraganglioma/tratamiento farmacológico , Adulto , Persona de Mediana Edad , Neoplasias de las Glándulas Suprarrenales/diagnóstico por imagen , Neoplasias de las Glándulas Suprarrenales/radioterapia , Anciano , Adulto Joven , Resultado del Tratamiento , Adolescente , Radioisótopos de YodoRESUMEN
OBJECTIVE: 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). METHODS: 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 150 mCi (5.55 GBq) of I-131 MIBG. We evaluated the first MIBG treatment and repeated MIBG treatments performed within 200 days 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. RESULTS: 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. CONCLUSION: In I-131 MIBG therapy for PPGLs, multiple administrations significantly increased only Grade 1 or 2 lymphopenia and leukopenia compared to single administration.
Asunto(s)
3-Yodobencilguanidina , Neoplasias de las Glándulas Suprarrenales , Paraganglioma , Feocromocitoma , Humanos , 3-Yodobencilguanidina/efectos adversos , 3-Yodobencilguanidina/uso terapéutico , Feocromocitoma/radioterapia , Estudios Retrospectivos , Masculino , Femenino , Paraganglioma/radioterapia , Persona de Mediana Edad , Adulto , Neoplasias de las Glándulas Suprarrenales/radioterapia , Anciano , Resultado del Tratamiento , Adulto JovenRESUMEN
PURPOSE OF REVIEW: More than a century since its discovery, the pathogenesis of Chagas heart disease (CHD) remains incompletely understood. The role of derangements in the autonomic control of the heart in triggering malignant arrhythmia before the appearance of contractile ventricular impairment was reviewed. RECENT FINDINGS: Although previous investigations had demonstrated the anatomical and functional consequences of parasympathetic dysautonomia upon the heart rate control, only recently, coronary microvascular disturbances and sympathetic denervation at the ventricular level have been reported in patients and experimental models of CHD, exploring with nuclear medicine methods their impact on the progression of myocardial dysfunction and cardiac arrhythmias. More important than parasympathetic impaired sinus node regulation, recent evidence indicates that myocardial sympathetic denervation associated with coronary microvascular derangements is causally related to myocardial injury and arrhythmia in CHD. Additionally, 123I-MIBG imaging is a promising tool for risk stratification of progression of ventricular dysfunction and sudden death.
Asunto(s)
Cardiomiopatía Chagásica , Simpatectomía , Humanos , Simpatectomía/métodos , Cardiomiopatía Chagásica/fisiopatología , Cardiomiopatía Chagásica/cirugía , Cardiomiopatía Chagásica/complicaciones , Arritmias Cardíacas/etiología , Arritmias Cardíacas/fisiopatología , Corazón/inervación , Corazón/diagnóstico por imagen , 3-Yodobencilguanidina , Sistema Nervioso Simpático/fisiopatologíaRESUMEN
ABSTRACT: 123I-meta-iodobenzylguanidine (123I-MIBG) is extensively used for initial staging and response evaluation in children with neuroblastoma. Physiological uptake of 123I-MIBG occurs in the salivary glands, liver, adrenal gland, myocardium, bowel, and thyroid gland. 123I-MIBG cannot cross an intact blood-brain barrier. We present the rare case of a 3-year-old boy with neuroblastoma and meningeal metastases who underwent an 123I-MIBG scan for disease restaging that showed abnormal brain uptake. Abnormal MIBG uptake in the brain can occur if there is disruption of the blood-brain barrier either secondary to metastases or after damage to blood-brain barrier.