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In previous studies of human T-lymphotropic virus type 1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), areas of slow blood flow in the spinal cord were related to pathological changes. While the pathological changes in the brain are milder than those in the spinal cord, they are also more significant in sites with slow blood flow. In this study, we investigated brain glucose metabolism in slow blood flow areas using fluorine-18 fluorodeoxyglucose positron emission tomography ((18)F-FDG-PET). Clinical features and brain (18)F-FDG-PET parameters were analyzed in six patients with HAM/TSP. For comparison of PET data, eight healthy volunteers were enrolled as normal controls (NLs). Glucose metabolism in the watershed areas of the middle and posterior cerebral arteries, as compared with that in the occipital lobes as a control, was significantly lower in HAM/TSP patients than in NLs. This result confirmed the relationship between slow blood flow areas and hypometabolism in HAM/TSP, and is consistent with previous findings that pathological changes are accentuated in sites with slow blood flow.
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Encéfalo/metabolismo , Glucosa/metabolismo , Paraparesia Espástica Tropical/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Velocidad del Flujo Sanguíneo/fisiología , Encéfalo/diagnóstico por imagen , Arterias Cerebrales/metabolismo , Circulación Cerebrovascular/fisiología , Femenino , Fluorodesoxiglucosa F18 , Humanos , Masculino , Persona de Mediana Edad , Imagen Multimodal , Paraparesia Espástica Tropical/diagnóstico , Paraparesia Espástica Tropical/diagnóstico por imagen , Tomografía de Emisión de Positrones , Radiofármacos , Flujo Sanguíneo Regional/fisiología , Estudios Retrospectivos , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Cardiac 123I-metaiodobenzylguanidine scintigraphy (MIBG) previously demonstrated an uptake reduction in patients with Parkinson's disease (PD). However, epidemiologic research showed that electrocardiography (ECG) abnormalities occurred prior to motor signs in PD. Here we investigated whether the electrical conduction system of the heart was impaired in PD. METHODS: Clinical features, ECG and MIBG parameters were analyzed in 191 patients with PD, 42 with multiple system atrophy (MSA) and 124 normal controls (NL). RESULTS: The PR interval was significantly longer in patients with PD than in NL. The PR interval was significantly negatively correlated with early and delayed heart-to-mediastinum ratios in MIBG scintigraphy in PD and MSA patients. In 19 PD patients with PR prolongation, 17 patients also had abnormal MIBG findings, and the other 2 showed normal MIBG. CONCLUSIONS: The PR prolongation must show some sympathetic system abnormality because it is mainly controlled by the sympathetic nervous system. PR prolongation supports the objective biomarker value of MIBG for PD diagnosis.
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Arritmias Cardíacas/diagnóstico por imagen , Sistema de Conducción Cardíaco/anomalías , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/diagnóstico por imagen , 3-Yodobencilguanidina , Anciano , Arritmias Cardíacas/etiología , Síndrome de Brugada , Trastorno del Sistema de Conducción Cardíaco , Electrocardiografía , Femenino , Sistema de Conducción Cardíaco/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Imagen de Perfusión Miocárdica/métodos , RadiofármacosRESUMEN
PURPOSE: The Cingulate Island score (CIScore) is useful index for differentiating between dementia with Lewy body (DLB) and Alzheimer's disease (AD) using regional cerebral blood flow (rCBF) SPECT. The Z score standing for medial temporal lobe (MTL) atrophy and the ratio of Z score between dorsal brain stem (DBS) to MTL are useful indices for differentiating between DLB and AD using MRI with VSRAD. The current study investigated the diagnostic ability by the combined use of rCBF SPECT and MRI in the differentiation between AD and DLB. MATERIALS AND METHODS: In cases with 42 AD and 28 DLB undertaken Tc-99m-ECD SPECT and MRI, we analyzed differential diagnostic ability between AD and DLB among following conditions by single or combined settings. Namely, they were (1) the CIScore as a parameter of rCBF SPECT (DLB ⦠0.25), (2) Z score value of MTL atrophy (DLB ⦠2.05), (3) the ratio of Z score of DBS to medial temporal gray matter as a parameter of brain atrophy using VSRAD (DLB ⧠0.38). Also, we analyzed them both including and omitting the elderly (over 75 years old). RESULTS: The accuracy of differential diagnosis in this condition was 74% for (1), 69% for (2), and 67% for (3). The accuracy by combination condition was 84% for (1) and (2), 81% for (1) and (3), and 67% for (2) and (3), respectively. The combination method by CIScore and the Z score of MTL showed the best accuracy. When we confined condition to ages younger than 75 years, the accuracy improved to 94% in the combination method. CONCLUSION: The combined use of CIScore and Z score of MTL was suggested to be useful in the differential diagnosis between DLB and AD particularly in younger than 75 years old.
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OBJECTIVE: The mechanisms underlying abdominal aortic aneurysm development remain unknown. We hypothesized that acceleration of glucose metabolism with the upregulation of glucose transporters is associated with abdominal aortic aneurysm development. METHODS AND RESULTS: Enhanced accumulation of the modified glucose analogue 18 fluoro-deoxyglucose by positron emission tomography imaging in the human abdominal aortic aneurysm was associated with protein expressions of glucose transporters-1 and -3, assessed by Western blot. The magnitude of glucose transporter-3 expression was correlated with zymographic matrix metalloproteinase-9 activity. Intraperitoneal administration of glycolysis inhibitor with 2-deoxyglucose significantly attenuated the dilatation of abdominal aorta induced by periaortic application of CaCl(2) in C57BL/6J male mice or reduced the aneurysmal formation in angiotensin II-infused apolipoprotein E knockout male mice. In monocytic cell line induced by phorbol 12-myristate 13-acetate or ex vivo culture obtained from human aneurysmal tissues, 2-deoxyglucose abrogated the matrix metalloproteinase-9 activity and interleukin-6 expression in these cells/tissues. Moreover, 2-deoxyglucose attenuated the survival/proliferation of monocytes and the adherence of them to vascular endothelial cells. CONCLUSIONS: This study suggests that the enhanced glycolytic activity in aortic wall contributes to the pathogenesis of aneurysm development. In addition, pharmacological intervention in glycolytic activity might be a potential therapeutic target for the disorder.
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Aorta Abdominal/efectos de los fármacos , Aneurisma de la Aorta Abdominal/prevención & control , Desoxiglucosa/administración & dosificación , Proteínas Facilitadoras del Transporte de la Glucosa/metabolismo , Glucólisis/efectos de los fármacos , Angiotensina II , Animales , Aorta Abdominal/metabolismo , Aorta Abdominal/patología , Aneurisma de la Aorta Abdominal/inducido químicamente , Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Aneurisma de la Aorta Abdominal/genética , Aneurisma de la Aorta Abdominal/metabolismo , Aneurisma de la Aorta Abdominal/patología , Apolipoproteínas E/deficiencia , Apolipoproteínas E/genética , Western Blotting , Cloruro de Calcio , Adhesión Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Fluorodesoxiglucosa F18/metabolismo , Proteínas Facilitadoras del Transporte de la Glucosa/genética , Transportador de Glucosa de Tipo 1/metabolismo , Transportador de Glucosa de Tipo 3/metabolismo , Humanos , Mediadores de Inflamación/metabolismo , Inyecciones Intraperitoneales , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Masculino , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Monocitos/efectos de los fármacos , Monocitos/metabolismo , Tomografía de Emisión de Positrones , Radiofármacos/metabolismo , Acetato de Tetradecanoilforbol/farmacología , Factores de Tiempo , Células U937 , Regulación hacia ArribaAsunto(s)
Disección Aórtica/diagnóstico por imagen , Fluorodesoxiglucosa F18/farmacocinética , Tomografía de Emisión de Positrones/métodos , Anciano de 80 o más Años , Humanos , Inflamación/diagnóstico por imagen , Inflamación/metabolismo , Masculino , Factores de Tiempo , Enfermedades Vasculares/diagnóstico por imagen , Enfermedades Vasculares/patologíaRESUMEN
BACKGROUND/PURPOSE: Previous FDG-PET studies have indicated neuroplasticity in the adult auditory cortex in cases of postlingual deafness. In the mature brain, auditory deprivation decreased neuronal activity in primary auditory and auditory-related cortices. In order to reevaluate these issues, we used statistical analytic software, namely a three-dimensional stereotaxic region of interest template (3DSRT), in addition to statistical parametric mapping (SPM; Institute of Neurology, University College of London, UK). MATERIALS AND METHODS: (18)F-FDG brain PET scans were performed on 7 postlingually deaf patients and 10 healthy volunteers. Significant increases and decreases of regional cerebral glucose metabolism in the patient group were estimated by comparing their PET images with those of healthy volunteers using SPM analysis and 3DSRT. RESULTS: SPM revealed that the glucose metabolism of the deaf patients was lower in the right superior temporal gyrus, both middle temporal gyri, left inferior temporal gyrus, right inferior lobulus parietalis, right posterior cingulate gyrus, and left insular cortex than that of the control subjects. 3DSRT data also revealed significantly decreased glucose metabolism in both primary auditory cortices of the postlingually deaf patients. CONCLUSION: SPM and 3DSRT analyses indicated that glucose metabolism decreased in the primary auditory cortex of the postlingually deaf patients. The previous results of PET studies were confirmed, and our method involving 3DSRT has proved to be useful.
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Corteza Auditiva/diagnóstico por imagen , Corteza Auditiva/metabolismo , Sordera/diagnóstico por imagen , Sordera/metabolismo , Glucosa/metabolismo , Tomografía de Emisión de Positrones/métodos , Adulto , Edad de Inicio , Anciano , Implantación Coclear , Femenino , Fluorodesoxiglucosa F18 , Lateralidad Funcional/fisiología , Humanos , Masculino , Persona de Mediana Edad , Plasticidad Neuronal/fisiología , Radiofármacos , Lóbulo Temporal/diagnóstico por imagen , Lóbulo Temporal/metabolismoRESUMEN
PURPOSE: We evaluated the reproducibility calculating volume-based FDG-PET/CT parameters, i.e., metabolic tumor volume (MTV) and total lesion glycolysis (TLG), in soft tissue tumors. MATERIALS AND METHODS: Fifty-three cases with soft tissue tumors were analyzed retrospectively. The conditions determining the lower limit of MTV were fixed value SUV 2.5 or 30% of SUVmax. To investigate the agreement of the measurements by two radiologists, %difference, the correlation coefficients and Bland-Altman plot were analyzed. We compared these parameters in both intra- and inter-operator for evaluating the agreement in the measurements. RESULTS: The values of % difference were excellent, 0.2-3.5%, in the intra-operator in all calculated volume-based parameters. In both inter- and intra-operator analysis, the values of % differences were lower in the parameters calculated by SUV 2.5 fixed value as a lower threshold compared with those calculated by 30% of SUVmax as a lower threshold. The correlation coefficient in MTV30% for inter-operator were 0.84 or 0.87, those were lower than values by the intra-operator evaluation. Nevertheless, the correlation coefficients were higher than 0.84 in every parameter. Particularly, correlation coefficient in the parameters calculated by SUV 2.5 fixed value was better than those calculated by 30% of SUVmax. The Bland-Altman plot analysis showed good agreement for all parameters, particularly in the intra-operator examinations. However, in the inter-operator study, some variances were noted in every condition. CONCLUSION: In conclusion, the reproducibility of measuring volume-based FDG-PET/CT parameters of soft tissue tumors was good, particularly, in the measurement by fixed lower limit value SUV 2.5 in the intra-operator.
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Fluorodesoxiglucosa F18 , Tomografía Computarizada por Tomografía de Emisión de Positrones , Humanos , Carga Tumoral , Estudios Retrospectivos , Reproducibilidad de los Resultados , Glucólisis , Pronóstico , RadiofármacosRESUMEN
PURPOSE: To assess the role of positron emission tomography-computed tomography (PET-CT) and multidetector-row CT (MD-CT) in detecting the primary lesion and lymph node metastasis in patients with colorectal cancers. METHODS: A collective total of 80 lesions resected from 77 patients were examined pathologically. We analyzed the significance of the standardized uptake value (SUV) and its relationship with the clinicopathologic findings of primary lesions and lymph node metastasis. The detectability of primary lesions and lymph node metastases on PET-CT images was compared with that on MD-CT images. RESULTS: The detectability of primary lesions was better on PET-CT images than on MD-CT images (p = 0.0023). We observed no significant differences in the SUV with respect to staging, tumor grade, lymphatic or vessel invasion, and macroscopic type; however, primary tumor size analysis revealed that tumors larger than 3 cm had a higher SUV than those smaller than 3 cm. The sensitivity of PET-CT for detecting lymph node metastasis was lower than that of MD-CT, but the specificity of PET-CT was higher than that of MD-CT. CONCLUSIONS: The SUV of primary cancers tends to increase in proportion to tumor size. Although the value of PET-CT in detecting lymph node metastasis is limited, PET -positive lymph nodes can be considered metastatic.
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Adenocarcinoma/diagnóstico por imagen , Neoplasias Colorrectales/diagnóstico por imagen , Fluorodesoxiglucosa F18 , Tomografía Computarizada Multidetector , Imagen Multimodal , Tomografía de Emisión de Positrones , Radiofármacos , Tomografía Computarizada por Rayos X , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/patología , Femenino , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Invasividad Neoplásica , Estadificación de Neoplasias , Sensibilidad y Especificidad , Carga TumoralRESUMEN
Introduction: Deep brain stimulation (DBS) is an effective treatment for advanced Parkinson's disease (PD) with the targeting bilateral subthalamic nucleus or globus pallidus internus (STN or GPi-DBS). So far, detailed studies on the efficacy of unilateral STN-DBS for motor symptoms have been reported, but few studies have been conducted on unilateral GPi-DBS. Materials and Methods: Seventeen patients with Parkinson's disease (PwPD) who underwent unilateral GPi-DBS were selected. We conducted comparison analyses between scores obtained 6-42 months pre- and postoperatively using the following measurement tools: the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III, the Hoehn and Yahr stage, the presence/absence of dyskinesia, Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB), Geriatric Depression Scale (GDS), levodopa equivalent dose (LED), and cerebral blood flow by single photon emission computed tomography (SPECT). Patient backgrounds were compared between four cohorts with favorable (good responders, ≥50% improvement) and unfavorable (poor responders, <50% improvement) postoperative outcome. Results: Significant improvement was observed postoperatively in the following: total MDS-UPDRS Part III scores during the off period, contralateral scores, ipsilateral scores, and axial scores. Similarly, the Hoehn and Yahr stages during the off period, and GDS also showed significant decrease. In contrast, LED, MMSE, and FAB remained unchanged while the number of patients who scored positive for dyskinesia decreased by 40%. Abnormal cerebral blood flow preoperatively seen in the cerebral cortex had normalized in the total score-based good responder cohort. In the ipsilateral score-based good responder cohort, cerebral blood flow increased in the contralateral frontal lobe including in the premotor cortex, contralateral to the DBS. Compared to the poor responders, postoperative good responders demonstrated significantly higher preoperative MMSE scores. Discussion: Unilateral GPi-DBS therapy was effective in improving contralateral, ipsilateral, and axial motor symptoms of patients with advanced PD; in particular, it was found to be especially beneficial in PwPD whose cognitive function was unimpaired; the treatment efficacy rivaled that of bilateral counterparts up till at least 6 months postoperatively. Finally, normalization of preoperative abnormalities in cerebral blood flow and increased cerebral blood flow in the contralateral frontal lobe indicated the beneficial potential of this therapy on ipsilateral motor symptoms.
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PURPOSE: The Cingulate Island Sign score (CIScore) by rCBF SPECT is used in the differentiation between Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) but has some false-positive AD cases. To resolve the problem, we developed new differential diagnosing method incorporating occipital lobe and para-hippocampal rCBF. MATERIALS AND METHODS: In 27 DLB and 31 AD cases undertaken Tc-99 m-ECD SPECT, we evaluated the mean Z score in the bilateral superior, middle, inferior occipital gyri, cuneus, amygdala, hippocampus, and para-hippocampus. One criterion of DLB was defined as the case with CIScore lower than 0.27. The other criteria were the cases of following either or both two conditions were satisfied. (1) The number of occipital gyri with mean Z score higher than 1 is three or more. (2) The number of hippocampal regions with mean Z score higher than 1 is one or less. We compared the differential diagnostic ability among these four criterions. RESULTS: The diagnostic accuracy by CIscore was 69% and that of the occipital gyri analysis 84%, para-hippocampal regions analysis 76% and combined occipital gyri and para-hippocampal regions analysis 93%. CONCLUSION: The new method by combined rCBF analysis of occipital gyri and para-hippocampal regions showed best diagnostic ability in differentiating DLB from AD.
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Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad por Cuerpos de Lewy/diagnóstico por imagen , Tomografía Computarizada de Emisión de Fotón Único , Anciano , Anciano de 80 o más Años , Encéfalo/irrigación sanguínea , Encéfalo/efectos de los fármacos , Circulación Cerebrovascular , Diagnóstico Diferencial , Femenino , Humanos , TecnecioRESUMEN
OBJECTIVE: The aim of this multicenter prospective study was to compare the sensitivity of 18F-fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography (PET/CT) with that of 67Ga single photon emission computed tomography (SPECT) for the identification of the site of greatest importance for the final diagnosis of the cause of fever of unknown origin (FUO). METHODS: The study participants consisted of patients with an axillary temperature ≥ 38.0 °C on ≥ 2 occasions within 1 week, with repeated episodes for ≥ 2 weeks prior to providing consent, and whose final diagnosis after undergoing specific examinations, including a chest-to-abdomen CT scan, was uncertain. All the patients underwent FDG-PET/CT imaging first, followed by 67Ga-SPECT imaging within 3 days. The results of the FDG-PET/CT and 67Ga-SPECT examinations were reviewed by the central image interpretation committee (CIIC), which was blinded to all other clinical information. The sensitivities of FDG-PET/CT and 67Ga-SPECT were then evaluated with regard to identifying the site of greatest importance for a final diagnosis of the cause of the fever as decided by the patient's attending physician. The clinical impacts (four grades) of FDG-PET/CT and 67Ga-SPECT on the final diagnosis were evaluated. RESULTS: A total of 149 subjects were enrolled in this study between October 2014 and September 2017. No adverse events were identified among the enrolled subjects. Twenty-one subjects were excluded from the study because of deviations from the study protocol. Among the 128 remaining subjects, a final diagnosis of the disease leading to the appearance of FUO was made for 92 (71.9%) subjects. The final diagnoses in these 92 cases were classified into four groups: noninfectious inflammatory disease (52 cases); infectious disease (31 cases), malignancy (six cases); and other (three cases). These 92 subjects were eligible for inclusion in the study's analysis, but one case did not meet the PET/CT image acquisition criteria; thus, PET/CT results were analyzed for 91 cases. According to the patient-based assessments, the sensitivity of FDG-PET/CT (45%, 95% CI 33.1-58.2%) was significantly higher than that for 67Ga-SPECT (25%, 95% CI 15.5-37.5%) (P = 0.0029). The clinical impact of FDG-PET/CT (91%) was also significantly higher than that for 67Ga-SPECT (57%, P < 0.001). CONCLUSIONS: FDG-PET/CT showed a superior sensitivity to 67Ga-SPECT for the identification of the site of greatest importance for the final diagnosis of the cause of FUO.
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Fiebre de Origen Desconocido/diagnóstico por imagen , Fluorodesoxiglucosa F18 , Radioisótopos de Galio , Tomografía Computarizada por Tomografía de Emisión de Positrones , Adulto , Femenino , Humanos , Japón , Masculino , Persona de Mediana EdadRESUMEN
PURPOSE: The current study was done to evaluate the usefulness of predicting capability of FDG PET/CT indices in therapeutic response of malignant tumor. METHODS: Series of FDG PET/CT were performed at both pre- and after therapy for 70 lesions of 58 patients with malignant tumor. Three months after the 2nd PET/CT, follow up CT was performed for determining the final therapeutic effect. We calculated various indices including SUVmax, the metabolic volume (MV) and the total lesion glycolysis (TLG). We calculated four kinds of indices, TLG50, TLG75, MV50 and MV75 based on the different threshold. Then we calculated deltaSUVmax, deltaMV50, deltaMV75, deltaTLG50 and deltaTLG75 from a change of these indices. Finally, we compared the predictive capability of these five indices in therapeutic response of malignant tumor. RESULTS: In the cancer therapy effect prediction, both deltaTLG75 and deltaTLG50 were significantly higher than SUVmax by using receiver operating-characteristic (ROC) curve analysis. The prognostic capability of deltaSUVmax for therapeutic response with sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 85.7%, 59.5%, 58.5%, 86.2% and 70.0%; deltaTLG75 96.4%, 69.0%, 67.5%, 96.7% and 80.0%; and deltaTLG50 96.4%, 76.2%, 73.0%, 97.0% and 84.3%, respectively. By the use of deltaTLG75 or deltaTLG50, the predictive ability for therapeutic response improved significantly compared to that by the use of deltaSUVmax. CONCLUSION: In the prediction for therapeutic response of various cancers by using FDG PET/CT, Total lesion glycolysis (TLG) was the most useful index.
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Glucólisis , Neoplasias/diagnóstico por imagen , Neoplasias/metabolismo , Tomografía de Emisión de Positrones , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Femenino , Fluorodesoxiglucosa F18 , Humanos , Masculino , Persona de Mediana Edad , RadiofármacosRESUMEN
Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) are two major types of dementia. Due to shared signs and symptoms, accurate diagnosis of these dementia subtypes is a clinical challenge. We assessed the sensitivity and specificity of the combined use of neuropsychological testing and brain imaging data for the differential diagnosis of these conditions. The study population included 77 patients with either AD or DLB. Ala score was calculated from Mini-Mental State Exam subscores, and the cingulate island sign score (CIScore) was obtained from image analysis of brain perfusion single-photon emission computed tomography. Correlation between Ala score and CIScore values was observed in the subgroup of patients aged ≤79 years (r = 0.485, P = 0.002), and the scatter plot revealed that 70% of DLB patients were within the range of cut-off values for DLB. In the group aged ≥80 years, there was poor correlation between the Ala and CIScores (r = 0.285, P = 0.083), the average CIScore exceeded the cut-off value, and the scatter plot showed lower sensitivity, illustrating the challenge of discriminating AD from DLB in an older patient population. The concurrent use of Ala score and CIScore enhanced the specificity and the area under the curve in both subgroups, indicating the improved ability of these tests to aid in the differential diagnosis of AD from DLB. Our findings suggest that the use of these methodologies in routine medical practice may increase the sensitivity and specificity of the diagnosis of dementia subtypes.
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Enfermedad de Alzheimer/diagnóstico , Enfermedad por Cuerpos de Lewy/diagnóstico , Pruebas Neuropsicológicas , Tomografía Computarizada de Emisión de Fotón Único , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/diagnóstico por imagen , Diagnóstico Diferencial , Femenino , Humanos , Enfermedad por Cuerpos de Lewy/diagnóstico por imagen , Masculino , Sensibilidad y EspecificidadRESUMEN
UNLABELLED: When a therapeutic drug is competitively displaced at the binding sites of serum proteins, the free fraction of the drug will be increased, with an increase in the manifestation of pharmacologic properties. In the case of molecular imaging probes, total clearance and tissue distribution are increased in such circumstances. The aim of this study was to observe the increase in cerebral accumulation of N-isopropyl-p-(123)I-iodoamphetamine ((123)I-IMP) using the protein-binding displacement method with amino acid infusion. METHODS: (123)I-IMP binding to human serum was investigated and identified. In addition, protein-binding sites and the specific binding sites of human serum albumin (HSA) and alpha(1)-acid glycoprotein (AGP) were examined by ultrafiltration. Then, serum-binding sites and the displacement effects of amino acid infusion, including Proteamin 12X Injection and Kidomin, were confirmed in vitro. Subsequently, displacement of (123)I-IMP serum protein binding with Proteamin amino acid infusion was tested in monkeys. A scintigraphic study of (123)I-IMP in monkeys loaded with or without Proteamin was performed, and time-activity-curves of (123)I-IMP brain accumulation in monkeys were evaluated. RESULTS: (123)I-IMP was bound to HSA site II and AGP to nearly equal extents. Compared with control conditions, loading with Proteamin and Kidomin markedly increased free fractions of binding site markers for HSA site II ((14)C-diazepam: 0.95% +/- 0.04% for control, 1.40% +/- 0.06% for Proteamin, 1.62% +/- 0.05% for Kidomin) and AGP ((3)H-propranolol: 10.60% +/- 0.32% for control, 13.18% +/- 0.14% for Proteamin, 13.82% +/- 0.72% for Kidomin). Amino acid infusions were thus suitable for use as displacers for binding site II and AGP. With use of Proteamin amino acid infusion to displace protein binding, the free fraction of (125)I-IMP (14.95% +/- 0.74%) was significantly increased in serum (19.24% +/- 0.87%). In a (123)I-IMP scintigraphic study of monkeys, average cerebral uptake in 2 monkeys increased by 1.34-fold with Proteamin. Our findings suggested that Proteamin treatment increased the free fraction of (123)I-IMP, yielding rapid and pronounced cerebral accumulation in vivo. CONCLUSION: Amino acid infusion can improve brain accumulation by competitive displacement of serum protein binding in vivo. Further similar studies are needed with other radiopharmaceuticals.
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Aminoácidos/administración & dosificación , Proteínas Sanguíneas/química , Proteínas Sanguíneas/metabolismo , Encéfalo/metabolismo , Yofetamina/química , Yofetamina/farmacocinética , Animales , Encéfalo/diagnóstico por imagen , Haplorrinos , Infusiones Intraarteriales , Unión Proteica/efectos de los fármacos , Cintigrafía , Radiofármacos/química , Radiofármacos/farmacocinéticaRESUMEN
INTRODUCTION: The binding of radiopharmaceutical to serum proteins is thought to be an important factor that restricts its excretion and accumulation in tissue. We calculated the effect of inhibitors of serum protein binding using a hypothetical radiopharmaceutical. In vitro experiments and protein binding inhibitor-loaded monkey scintigraphy were then conducted using (123)I-N-isopropyl-p-iodoamphetamine (IMP) as the radiopharmaceutical. METHODS: Free fraction ratios of radiopharmaceutical were calculated with one radiopharmaceutical, two serum proteins and two specific inhibitors in the steady state at various serum protein concentrations. In vitro protein binding inhibition studies using human, rat and monkey sera were performed with site-selective displacers of specific binding sites: 400 microM 6-methoxy-2-naphthylacetic acid (6MNA; a major nabumeton metabolite) as a serum albumin Site II inhibitor and 400 microM erythromycin (ETC) as an alpha(1)-acid glycoprotein (AGP) site inhibitor. Scintigraphy with or without 6MNA loading of monkeys was performed. RESULTS: The theoretical findings roughly corresponded to the experimental results. Approximately 75% of IMP bound to serum albumin Site II and AGP in the species examined. The free fraction of IMP (25.0+/-0.6% for human, 22.8+/-0.4% for monkey, 23.7+/-0.3% for rat) increased with loading of specific protein binding inhibitors (6MNA: 28.0+/-0.3% for human, 24.5+/-0.7% for monkey, 24.3+/-0.2% for rat; ETC: 26.3+/-0.4% for human, 29.5+/-1.1% for monkey, 26.0+/-0.7% for rat) and was serum protein concentration dependant based on the results of calculations. Simultaneous administration of 6MNA and ETC produced a higher free fraction ratio of IMP (31.9+/-1.0% for human, 34.6+/-0.4% for monkey, 27.0+/-0.3% for rat) than summation of the single administrations of 6MNA and ETC (domino effect) in human, rat and monkey sera. Rapid cerebral accumulation was observed with 6MNA loading in monkey scintigraphy. CONCLUSIONS: 6MNA appears to change the pharmacokinetics and brain accumulation of IMP in monkeys. Further studies in human are required.
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Proteínas Sanguíneas/metabolismo , Yofetamina/metabolismo , Modelos Biológicos , Radiofármacos/metabolismo , Animales , Sitios de Unión , Unión Competitiva , Proteínas Sanguíneas/antagonistas & inhibidores , Proteínas Sanguíneas/química , Interacciones Farmacológicas , Eritromicina/administración & dosificación , Eritromicina/metabolismo , Eritromicina/farmacología , Femenino , Haplorrinos/metabolismo , Humanos , Inyecciones Intravenosas , Yofetamina/sangre , Yofetamina/farmacocinética , Ligandos , Ácidos Naftalenoacéticos/administración & dosificación , Ácidos Naftalenoacéticos/metabolismo , Ácidos Naftalenoacéticos/farmacología , Orosomucoide/antagonistas & inhibidores , Orosomucoide/química , Orosomucoide/metabolismo , Unión Proteica/efectos de los fármacos , Radiofármacos/sangre , Radiofármacos/farmacocinética , Ratas , Albúmina Sérica/antagonistas & inhibidores , Albúmina Sérica/química , Albúmina Sérica/metabolismo , Distribución Tisular/efectos de los fármacos , Imagen de Cuerpo EnteroRESUMEN
BACKGROUND: The deep-inspiration breath-hold F-fluorodeoxyglucose PET/computed tomography (DIBH F-FDG PET/CT) technique improves the limitations of diagnosing a lesion located in an area influenced by respiratory motion that brings about spatial misregistration caused by respiration between PET and CT. However, its clinical effectiveness with regard to abdominal lesions has not been elucidated. The influence of respiratory motion for calculating the maximal standardized uptake value (SUVmax) and metabolic volume (MV) in DIBH F-FDG PET/CT has not been investigated either. OBJECTIVE: The purpose of this study was to investigate the usefulness of the DIBH F-FDG PET/CT technique in diagnosing liver tumors, bile duct cancers, and pancreas tumors. In addition, we compared the values of SUVmax and MV between DIBH and nonbreath-hold (NBH). METHODS: Forty patients with various abdominal malignancies including liver tumors, bile duct cancers, and pancreas tumors were enrolled. In total, the patients had 47 abdominal lesions. All patients showed a misregistered image in the early whole-body image taken 50 min after intravenous F-FDG infusions. We added the delayed images 40 min after the first image. On the delayed image, we carried out both conventional techniques with normal respiration (NBH) and the DIBH technique. Finally, we compared two kinds of images in each patient. At the same time, we compared both SUVmax and MV of cancer obtained by the two kinds of imaging methods. RESULTS: In 14 lesions (29.8%), we corrected the anatomical tumor location, from the incorrect to the correct organ, by the DIBH technique. In 22 lesions (46.8%), we corrected the tumor location within the organ. Consequently, tumor staging also changed in 11 patients (23.4%) after correction by the DIBH technique. Regarding the SUVmax value by DIBH, it showed an increase of approximately 15.0-58.6% compared with that measured by NBH. In contrast, the value of MV by DIBH showed a decrease of 20% compared with that measured by NBH. CONCLUSION: The DIBH F-FDG PET/CT technique is feasible for accurate localization when diagnosing of liver tumors, bile duct cancers, and pancreas cancers. The DIBH technique also improves the inaccurate quantification of both SUVmax and MV.
Asunto(s)
Neoplasias de los Conductos Biliares/diagnóstico por imagen , Fluorodesoxiglucosa F18 , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pancreáticas/diagnóstico por imagen , Radiofármacos , Adulto , Anciano , Femenino , Humanos , Inhalación , Masculino , Persona de Mediana Edad , Movimiento , Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos XRESUMEN
Recent studies reported that high doses of short-acting loop diuretics are associated with poor outcomes in patients with heart failure (HF). Short-acting loop diuretics have been shown to activate the renin-angiotensin system (RAS) and have no favorable effects on cardiac sympathetic nervous system (SNS) activity. The goal of this study is to investigate the relationship between daily doses of furosemide and the outcomes of patients with left ventricular dysfunction (LVD) from the viewpoint of cardiac SNS abnormalities using iodine-123-labeled metaiodobenzylguanidine (l-MIBG) myocardial scintigraphy.We enrolled 137 hospitalized patients (62.5â±â14.2 years old, 103 men) with LVEF < 45% who underwent l-MIBG myocardial scintigraphy. A delayed heart-to-mediastinum ratio (delayed HMR) was assessed using l-MIBG scintigraphy. Cardiac events were defined as cardiac death or re-hospitalization due to the deterioration of HF. Cox proportional hazard analysis was used to identify predictors of cardiac events.Cardiac events occurred in 57 patients in a follow-up period of 33.1â±â30 months. In a multivariate Cox proportional hazard analysis, delayed HMR and furosemide doses were identified as independent predictors of cardiac events (Pâ=â.0042, Pâ=â.033, respectively). Inverse probability of treatment weighting Cox modeling showed that the use of furosemide (≥40âmg /day) was associated with cardiac events with a hazard ratio of 1.96 (Pâ=â.003). In the Kaplan-Mayer analysis, the cardiac event-free survival rate was significantly lower in patients treated with high doses of furosemide (≥60âmg/day vs 40-60âmg/day vs <40âmg/day, the Log-rank test Pâ<â.0001). In a receiver-operating characteristic (ROC) analysis, the cut-off value for cardiac events was 40âmg/day of furosemide. The cardiac event-free rate was significantly lower in patients with delayed HMR <1.8 (median value) and receiving furosemide ≥40âmg/day than in other patients (the Log-rank test Pâ<â.0001). Significant differences in cardiac event rates according to furosemide doses among patients with delayed HMR <1.8 were observed among patients without ß-blocker therapy (Pâ=â.001), but not among those with ß-blocker therapy (Pâ=â.127).The present results indicate that a relationship exists between higher doses of furosemide and poor outcomes. The prognosis of HF patients with severe cardiac SNS abnormalities receiving high-dose short-acting loop diuretics is poor.
Asunto(s)
Furosemida , Insuficiencia Cardíaca , Corazón , Sistema Nervioso Simpático/efectos de los fármacos , Disfunción Ventricular Izquierda , 3-Yodobencilguanidina/farmacología , Anciano , Disponibilidad Biológica , Relación Dosis-Respuesta a Droga , Femenino , Furosemida/administración & dosificación , Furosemida/efectos adversos , Furosemida/farmacocinética , Corazón/diagnóstico por imagen , Corazón/inervación , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/fisiopatología , Humanos , Japón , Masculino , Persona de Mediana Edad , Imagen de Perfusión Miocárdica/métodos , Evaluación de Procesos y Resultados en Atención de Salud , Radiofármacos/farmacología , Inhibidores del Simportador de Cloruro Sódico y Cloruro Potásico/administración & dosificación , Inhibidores del Simportador de Cloruro Sódico y Cloruro Potásico/efectos adversos , Inhibidores del Simportador de Cloruro Sódico y Cloruro Potásico/farmacocinética , Volumen Sistólico/efectos de los fármacos , Disfunción Ventricular Izquierda/diagnóstico , Disfunción Ventricular Izquierda/tratamiento farmacológicoRESUMEN
PURPOSE: Firstly, to assess the effect of percutaneous endoscopic gastrostomy (PEG) tube placement on gastric emptying, gastrointestinal (GI) tract motility and the rate of gastroesophageal reflux (GER). Secondly, to confirm whether correlations exist between drug absorption behaviour and GI tract motility using the combination method of absorption function analysis with the motility study. METHODS: Subjects comprised 11 patients with neurological dysphagia. Gastric-emptying scintigraphy was performed both before PEG via nasogastric tube feeding and after PEG placement. After fasting for more than 8 h, each patient was administered 111 MBq of 99mTc-labelled diethylenetriaminepentaacetic acid (DTPA) with a 100 ml liquid meal via a nutrition tube. Dynamic imaging was performed immediately after administration of a radiolabelled liquid meal for a 1 h period and static imaging was performed after 1, 2, 3 and 6 h. Gastric emptying half-time (T50) was calculated in each patient, and GER ratio and GI transit rate were also evaluated. Simultaneously, we administered 10 mg of famotidine in six of the 11 patients and measured serum concentrations of famotidine at 0, 1, 2, 3 and 6 h. Using the time-concentration curve of famotidine, the maximum concentration of famotidine (Cmax) and area under the curve of famotidine (AUCf) were calculated for each patient. RESULTS: In seven of 11 patients, T50 changed after PEG placement, but not significantly. The GER ratio was significantly decreased and complicated pneumonia improved after PEG placement. GI transit rate for each GI segment was unchanged after PEG placement. Significant linear correlations were identified between T50 and both Cmax and AUCf. CONCLUSION: Gastric-emptying scintigraphy with Tc-DTPA was effective in the evaluation of GI transit before and after PEG, as well as in assessing GER. Motility and famotidine absorption were maintained after PEG placement. Significant linear correlations were found between T50 and both Cmax and AUCf. These findings suggest that drug absorption may have some relationship between T50. The result may be more reliable with a larger population.
Asunto(s)
Endoscopía Gastrointestinal/efectos adversos , Vaciamiento Gástrico , Enfermedades Gastrointestinales/diagnóstico por imagen , Enfermedades Gastrointestinales/etiología , Motilidad Gastrointestinal , Gastrostomía/efectos adversos , Procedimientos Quirúrgicos Mínimamente Invasivos/efectos adversos , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , CintigrafíaRESUMEN
OBJECTIVE: The objective of the present study is to investigate the correlations across various types of interface software for (201)Tl gated myocardial perfusion SPECT (MPS) in calculating two common diastolic function parameters (DFx), peak-filling rates (PFR), and time-to-peak filling (TTPF). METHODS: A total of 109 patients (66 men and 43 women; age 35-78 years) were studied. All patients were classified into three groups (i.e., ND, no-defect group; SD, small-defect group; LD, large-defect group) to clarify the influence of perfusion defects possibly affecting the analysis. Two kinds of available software, namely, quantitative gated SPECT (QGS2) and perfusion and functional analysis for gated SPECT (pFAST2) with cardioGRAF were used to obtain PFR and TTPF. Finally, we analyzed the correlation between DFx obtained with the two different kinds of software. RESULTS: The values of LVEF, PFR, and TTPF were assessed in all patients. In both the ND (correlation coefficients were 0.92, 0.79, and 0.99, respectively) and SD groups (correlation coefficients were 0.74, 0.88, and 0.98, respectively), a strong correlation was observed. In contrast, PFR did not show a significant correlation in the LD group. CONCLUSIONS: With the two different kinds of software, QGS2 and pFAST2, the calculated PFR was almost equal and showed good correlations in both ND and SD groups. In contrast, the numerical value varied between the two methods, and its correlation was poor in the LD group. However, TTPF showed a good correlation regardless of the presence of perfusion defects, and the values were equal. TTPF was confirmed to be a stable diastolic index across the two kinds of software, QGS2 and pFAST2, in (201)Tl gated MPS.
Asunto(s)
Imagen de Acumulación Sanguínea de Compuerta/métodos , Validación de Programas de Computación , Radioisótopos de Talio/farmacocinética , Tomografía Computarizada de Emisión de Fotón Único/métodos , Función Ventricular Izquierda , Adulto , Anciano , Gasto Cardíaco , Diástole/fisiología , Femenino , Imagen de Acumulación Sanguínea de Compuerta/instrumentación , Ventrículos Cardíacos/diagnóstico por imagen , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Masculino , Persona de Mediana Edad , Válvula Mitral , Volumen Sistólico , Tomografía Computarizada de Emisión de Fotón Único/instrumentaciónRESUMEN
UNLABELLED: (123)I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy is a useful tool for differentiating idiopathic Parkinson's disease (PD) from parkinsonism (PS) caused by other disorders. However, cardiac MIBG uptake is affected by various causes. Alternatively, hypoperfusion in the occipital lobe of PD is reported recently. OBJECTIVE: The objective is to clarify the correlation between regional cerebral blood flow (rCBF) alteration and cardiac MIBG uptake in PD. In addition, we examined whether additional brain perfusion analysis improved the differential diagnostic ability for PD from PS when compared with MIBG scintigraphy alone. METHODS: Forty-nine patients with PD (27 mild groups: Hoehn and Yahr stages I, II; 22 severe groups: Hoehn and Yahr stages III, IV) and 28 patients with PS participated. We compared absolute rCBF values between PD and PS. In addition, we determined correlation between MIBG parameters and each rCBF value. Finally, we compared the diagnostic ability for the differentiation of PD from PS between two diagnostic criteria, each MIBG index abnormality alone [heart-to-mediastinum ratio, H/M (E) < 1.9, H/E (D) < 1.7, washout rate > 40%] and each MIBG index abnormality or occipital lobe hypoperfusion (<36 ml/100 g per min). RESULTS: Absolute rCBF value of occipital lobe was significantly lower in severe PD as compared with PS or mild PD. In the correlation analysis, rCBF of occipital lobe correlated positively with MIBG parameters (H/M). Regarding the diagnostic ability, sensitivity improved by accounting for occipital hypoperfusion as compared with MIBG indices alone. In contrast, neither specificity nor accuracy improved by adding occipital lobe analysis. CONCLUSIONS: MIBG parameters (H/M) correlated positively with occipital hypoperfusion in PD. In the differential diagnosis between PD and PS, although its usefulness might be limited, analysis of rCBF in the occipital lobe added to (123)I-MIBG myocardial imaging can be recommended.