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1.
Appl Radiat Isot ; 157: 109019, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31889678

RESUMO

For the patients who underwent 18fluorinated para-boronophenylalanine (18FBPA) positron emission tomography (PET) and 18fluorodeoxyglucose (18FDG) PET within a period of 2 weeks, maximum standardized uptake value (SUVmax), tumor-to-normal tissue ratio (TNR), and tumor-to-blood ratio (TBR) for 18FBPA were compared with SUVmax for 18FDG. A total of 30 patients were selected for comparison. SUVmax for 18FBPA was correlated the best with SUVmax for 18FDG. Subsequently, the SUVmax correlation between 18FBPA and 18FDG were verified among 82 patients. The correlation factor was 0.4825.


Assuntos
Compostos de Boro/metabolismo , Fluordesoxiglucose F18/metabolismo , Melanoma/metabolismo , Fenilalanina/análogos & derivados , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Fenilalanina/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Adulto Jovem
2.
J Radiat Res ; 50(1): 51-60, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18957828

RESUMO

We evaluate the clinical results of a form of tumor selective particle radiation known as boron neutron capture therapy (BNCT) for newly-diagnosed glioblastoma (NDGB) patients, especially in combination with X-ray treatment (XRT). Between 2002 and 2006, we treated 21 patients of NDGB with BNCT utilizing sodium borocaptate and boronophenylalanine simultaneously. The first 10 were treated with only BNCT (protocol 1), and the last 11 were treated with BNCT followed by XRT of 20 to 30 Gy (protocol 2) to reduce the possibility of local tumor recurrence. No chemotherapy was applied until tumor progression was observed. The patients treated with BNCT (protocol 1 plus 2) showed a significant survival prolongation compared with the institutional historical controls. BNCT also showed favorable results in correspondence with the RTOG- and EORTC-RPA subclasses. The median survival time (MST) was 15.6 months for protocols 1 and 2 together. For protocol 2, the MST was 23.5 months. The main causes of death were cerebrospinal fluid dissemination as well as local recurrence. Our modified BNCT protocol showed favorable results of patients with NDGB not only for those with good prognoses but also for those with poor prognoses.


Assuntos
Terapia por Captura de Nêutron de Boro/métodos , Neoplasias Encefálicas/radioterapia , Glioblastoma/radioterapia , Adolescente , Adulto , Idoso , Neoplasias Encefálicas/diagnóstico , Terapia Combinada , Feminino , Glioblastoma/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
3.
Neurol Res ; 29(8): 830-4, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17716389

RESUMO

OBJECTIVE: To distinguish idiopathic-normal pressure hydrocephalus (i-NPH) from the elder with brain atrophy is difficult. This investigation was undertaken to determine the cerebral oxygen metabolism and the cerebral blood flow using positron emission tomography (PET) in patients with i-NPH. Comparison of the variables between i-NPH patients and the age-comparable control with asymptomatic ventricular dilatation were performed. METHODS: Nineteen patients were studied. Nine i-NPH patients with a mean age of 74.8 +/- 1.8 years (mean +/- SD) were examined using PET. The subjects who underwent a ventriculoperitoneal shunt (VPS) had the triad of NPH and ventricular dilatation on computed tomography (CT) and/or magnetic resonance imaging (MRI). The results of the PET study were compared with those for ten age-comparable controls (74.8 +/- 5.5 years) with asymptomatic ventricular dilatation and no severe cerebrovascular disease on MRI and magnetic resonance angiography (MRA). The PET study included analyses of regional cerebral blood flow (rCBF), regional cerebral blood volume (rCBV), regional oxygen extraction fraction (rOEF) and regional cerebral metabolic rate of oxygen (rCMRO(2)). RESULTS: In i-NPH, rCBF tended to decrease in the frontal lobe and the basal ganglia. rCMRO(2) in the frontal lobe of i-NPH was significantly higher than that in the controls (p<0.05 by Student's t-test), although rCMRO(2) in the basal ganglia of i-NPH was reduced. rCBV and rOEF showed no significant differences. CONCLUSION: Reduction of oxygen metabolism in the basal ganglia might be one of the factors causing symptoms in i-NPH. Particular pattern of cerebral oxygen metabolism in i-NPH was not obvious in the present study.


Assuntos
Encéfalo/metabolismo , Circulação Cerebrovascular/fisiologia , Hidrocefalia de Pressão Normal/metabolismo , Hidrocefalia de Pressão Normal/patologia , Oxigênio/metabolismo , Idoso , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagem , Encéfalo/cirurgia , Estudos de Casos e Controles , Feminino , Humanos , Hidrocefalia de Pressão Normal/diagnóstico por imagem , Hidrocefalia de Pressão Normal/cirurgia , Imageamento por Ressonância Magnética/métodos , Masculino , Tomografia por Emissão de Pósitrons/métodos , Fluxo Sanguíneo Regional/fisiologia , Tomografia Computadorizada por Raios X/métodos , Derivação Ventriculoperitoneal/métodos
4.
Int J Radiat Oncol Biol Phys ; 66(5): 1523-7, 2006 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-17056200

RESUMO

PURPOSE: To analyze the dose-volume histogram (DVH) of head-and-neck tumors treated with boron neutron capture therapy (BNCT) and to determine the advantage of the intra-arterial (IA) route over the intravenous (IV) route as a drug delivery system for BNCT. METHODS AND MATERIALS: Fifteen BNCTs for 12 patients with recurrent head-and-neck tumors were included in the present study. Eight irradiations were done after IV administration of boronophenylalanine and seven after IA administration. The maximal, mean, and minimal doses given to the gross tumor volume were assessed using a BNCT planning system. RESULTS: The results are reported as median values with the interquartile range. In the IA group, the maximal, mean, and minimal dose given to the gross tumor volume was 68.7 Gy-Eq (range, 38.8-79.9), 45.0 Gy-Eq (range, 25.1-51.0), and 13.8 Gy-Eq (range, 4.8-25.3), respectively. In the IV group, the maximal, mean, and minimal dose given to the gross tumor volume was 24.2 Gy-Eq (range, 21.5-29.9), 16.4 Gy-Eq (range, 14.5-20.2), and 7.8 Gy-Eq (range, 6.8-9.5), respectively. Within 1-3 months after BNCT, the responses were assessed. Of the 6 patients in the IV group, 2 had a partial response, 3 no change, and 1 had progressive disease. Of 4 patients in the IA group, 1 achieved a complete response and 3 a partial response. CONCLUSION: Intra-arterial administration of boronophenylalanine is a promising drug delivery system for head-and-neck BNCT.


Assuntos
Compostos de Boro/administração & dosagem , Terapia por Captura de Nêutron de Boro/métodos , Neoplasias de Cabeça e Pescoço/radioterapia , Recidiva Local de Neoplasia/radioterapia , Fenilalanina/agonistas , Adulto , Idoso , Idoso de 80 Anos ou mais , Compostos de Boro/farmacocinética , Feminino , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , Infusões Intra-Arteriais , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/metabolismo , Fenilalanina/farmacocinética , Resultado do Tratamento
5.
J Nucl Med ; 46(4): 553-9, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15809475

RESUMO

UNLABELLED: Left ventricular (LV) remodeling after myocardial infarction (MI) is a maladaptive process that increases the risk of heart failure and death. The myocardial phosphoinositide cycle, which is located downstream from several neurohumoral factors, plays a crucial role in LV remodeling. Our animal studies demonstrated that 1-[1-11C]butyryl-2-palmitoyl-rac-glycerol (11C-DAG) can be used to visualize regions with an activated phosphoinositide cycle. Therefore, we examined whether myocardial 11C-DAG accumulation assessed by PET is relevant to LV enlargement and systolic dysfunction in post-MI patients. METHODS: We performed PET with 11C-DAG in 13 post-anteroseptal MI patients and 4 healthy volunteers. We placed regions of interest on the noninfarcted myocardium and calculated the myocardium-to-left atrial (LA) chamber ratio of 11C-DAG accumulation. RESULTS: The myocardium-to-LA chamber ratio of 11C-DAG was significantly higher in the post-MI patients (mean +/- SD, 1.73 +/- 0.35) compared with that of the healthy volunteers (mean +/- SD, 1.25 +/- 0.13; P < 0.05). In the post-MI patients, the myocardium-to-LA chamber ratio of (11)C-DAG was significantly correlated with the LV end-diastolic volume index (r = 0.79, P < 0.01) and the plasma concentration of brain natriuretic peptide (r = 0.85, P < 0.001) and negatively correlated with the LV ejection fraction (r = -0.69, P < 0.01). CONCLUSION: These findings suggest that the myocardial 11C-DAG accumulation assessed by PET is relevant to LV enlargement, LV systolic dysfunction, and humoral activation in post-MI patients. This new imaging strategy based on intracellular signaling may contribute to the assessment and treatment of post-MI patients.


Assuntos
Glicerídeos/farmacocinética , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/metabolismo , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/metabolismo , Remodelação Ventricular/fisiologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/complicações , Cintilografia , Compostos Radiofarmacêuticos/farmacocinética , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Estatística como Assunto , Disfunção Ventricular Esquerda/etiologia
6.
Oncol Rep ; 14(4): 853-9, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16142342

RESUMO

To test the in vivo transport system and tumor proliferation of meningiomas, in comparison with gliomas, 25 patients with meningiomas and 8 gliomas underwent quantitative kinetic analysis of ([18F])fluoro-2-deoxy-D-glucose (FDG) - positron emission tomography (PET) imaging and immunohistochemical study. Kinetic analysis was obtained by calculation of the rate constants: K1 (ml/g/min), which represents the transport of FDG from plasma to tissue; k2 (min(-1)), which demonstrates the transport back from tissue to plasma; and k3 (min(-1)), an indicator of glucose metabolism, using Gjedde's plot methods in a three-compartment model. Surgical specimens were evaluated by means of three different methods: i) immunoreactivity to vascular endothelial growth factor (VEGF) and glucose transporter-1 (Glut-1), representing the permeability of tumor vessels; ii) immunostaining for von Willebrand Factor (vWF), reflecting vascular surface areas of arterioles; and iii) the MIB-1 labeling index (MIB-1 LI), representing the proliferative potential. K1 was higher in meningiomas than in gliomas and was higher in atypical than in benign meningiomas. k3 was correlated with MIB-1 LI in meningiomas, but not in gliomas. Immunohistochemically, meningiomas were less reactive to VEGF or Glut-1 than gliomas but atypical meningiomas stained more intensely than benign meningiomas. The vascular surface area was significantly larger in meningiomas than in gliomas and atypical meningiomas had high values for both permeability and surface area than benign meningiomas. High values for K1 and k3 indicate the aggressive proliferation of meningiomas and, in atypical meningiomas, the synergistic interaction of the high permeability and the large surface area yielded conditions conducive to glucose metabolism and tumor proliferation. Evaluation of K1 and k3 facilitates to predict the tumor aggressiveness and to optimize the surgical management.


Assuntos
Neoplasias Encefálicas/patologia , Meningioma/patologia , Neoplasias/patologia , Tomografia por Emissão de Pósitrons/métodos , Adulto , Idoso , Transporte Biológico , Neoplasias Encefálicas/metabolismo , Proliferação de Células , Feminino , Glioma/patologia , Transportador de Glucose Tipo 1/metabolismo , Humanos , Imuno-Histoquímica , Cinética , Masculino , Meningioma/metabolismo , Pessoa de Meia-Idade , Modelos Estatísticos , Invasividade Neoplásica , Permeabilidade , Fatores de Tempo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator de von Willebrand/metabolismo
7.
J Neurosurg ; 103(6): 1000-9, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16381186

RESUMO

OBJECT: To improve the effectiveness of boron neutron capture therapy (BNCT) for malignant gliomas, the authors used epithermal rather than thermal neutrons for deep penetration and two boron compounds-sodium borocaptate (BSH) and boronophenylalanine (BPA)-with different accumulation mechanisms to increase the boron level in tumors while compensating for each other's faults. METHODS: Thirteen patients, 10 of whom harbored a glioblastoma multiforme (GBM), one a gliosarcoma, one an anaplastic astrocytoma, and one an anaplastic oligoastrocytoma, were treated using this modified BNCT between January 2002 and December 2003. Postoperatively, neuroimaging revealed that only one patient with a GBM had no lesion enhancement postoperatively. The patients underwent 18F-BPA positron emission tomography, if available, to assess the accumulation and distribution of BPA before neutron radiotherapy. The neutron fluence rate was estimated using the Simulation Environments for Radiotherapy Applications dose-planning system before irradiation. The patients' volume assessments were performed using magnetic resonance (MR) imaging or computerized tomography (CT) scanning. Improvements in the disease as seen on neuroimages were assessed between 2 and 7 days after irradiation to determine the initial effects of BNCT; its maximal effects were also analyzed on serial neuroimages. The mean tumor volume before BNCT was 42.3 cm3. Regardless of the pre-BNCT tumor volume, in every patient harboring an assessable lesion, improvements on MR or CT images were recognized both at the initial assessment (range of volume reduction rate 17.4-71%, mean rate 46.4%) and at follow-up assessments (range of volume reduction rates 30.3-87.6%, mean rate 58.5%). More than 50% of the contrast-enhanced lesions disappeared in eight of the 12 patients during the follow-up period. CONCLUSIONS: This modified BNCT produced a good improvement in malignant gliomas, as seen on neuroimages.


Assuntos
Terapia por Captura de Nêutron de Boro/métodos , Neoplasias Encefálicas/radioterapia , Glioma/radioterapia , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Adulto , Idoso , Astrocitoma/radioterapia , Compostos de Boro/uso terapêutico , Terapia por Captura de Nêutron de Boro/efeitos adversos , Edema Encefálico/diagnóstico , Edema Encefálico/etiologia , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/patologia , Feminino , Glioblastoma/radioterapia , Glioma/complicações , Glioma/diagnóstico , Glioma/patologia , Gliossarcoma/radioterapia , Humanos , Masculino , Pessoa de Meia-Idade , Nêutrons , Resultado do Tratamento
8.
Clin Cancer Res ; 9(16 Pt 1): 5888-95, 2003 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-14676111

RESUMO

PURPOSE: Boron neutron capture therapy (BNCT) for the treatment of brain tumors has attracted attention recently, and its clinical application has been progressing. We have focused on the use of BNCT with 10B-boronophenylalanine, which preferentially delivers boron-10 atoms to malignant cells through the amino acid transport system. In the present study, we evaluated the long-term outcomes of treatments using 18F-10B-fluoroboronophenylalanine (FBPA), which is an analogue of 10B-boronophenylalanine, by investigating the prognostic significance of the metabolic values and ratios of FBPA as determined by positron emission tomography (PET) in patients with gliomas. EXPERIMENTAL DESIGN: Our subjects were 22 patients who underwent an FBPA-PET study and were followed for at least 4 months thereafter. PET parameters, such as the rate constants K1, k2, k3, and k4, were measured before treatment. Data regarding the tumors, the contralateral normal region, and the uptake ratio of FBPA between the tumor and normal tissue 40 min after injection of the tracer were compared with survival rates after the PET treatment. The survival time and the prognostic factors were tested using a Kaplan-Meier survival curve and Cox regression analysis, respectively. RESULTS: Among the clinical parameters, the histological grade of a tumor influences survival significantly. When the survival of patients with PET parameters or ratios above the median was compared with that of patients with parameters or ratios below the median, the most significant PET parameter was the K1 value of the tumor. Median survival in patients with a tumor K1 value of 0.033 ml/min (median value) or higher was 11 months, which was significantly shorter than the 77 months in patients with a K1 value below the median (P=0.0006 by generalized Wilcoxon test). CONCLUSIONS: The kinetic constants of FBPA metabolism as determined by PET can be of ancillary significance in predicting the prognosis and indicating the feasibility of BNCT in patients with gliomas. The mean survival time was significantly shorter in patients with high uptakes of FBPA. A contributing factor is the K1 value, which reflects amino acid transport activity. FBPA-PET images can allow clinicians to develop treatment plans that are better tailored to the clinical features of their patients.


Assuntos
Compostos de Boro/uso terapêutico , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/radioterapia , Glioma/diagnóstico por imagem , Glioma/radioterapia , Fenilalanina/análogos & derivados , Fenilalanina/uso terapêutico , Tomografia Computadorizada de Emissão , Adulto , Idoso , Terapia por Captura de Nêutron de Boro , Feminino , Radioisótopos de Flúor/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida , Resultado do Tratamento
9.
Nucl Med Commun ; 26(6): 519-25, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15891595

RESUMO

OBJECTIVE: Conventional methods of quantitative Na18F positron emission tomography require multiple arterial blood sampling in order to obtain the input function, and the procedures are invasive and complicated. This study aims to establish a simplified and reliable technique for obtaining the input function. METHODS: Multiple arterial blood sampling was performed on 12 persons. The time point for one-point sampling was determined as the time when (1) the plasma radioactivity obtained showed the highest correlation to the real integrated value, which was calculated from the input function, and (2) the coefficient of variation of the real integrated value divided by plasma radioactivity obtained at each time point became the minimum. Scaling factors were obtained in order to estimate the plasma radioactivity at each time point, and a reference table was produced in order to estimate the input function. RESULTS: The optimal timing for one-point sampling was 12 min after intravenous injection of Na18F. The estimated integrated value obtained from arterial blood sampling at 12 min and the reference table was highly correlated with the real integrated value (P<0.001). Levels of plasma radioactivity of arterial blood and venous blood were almost the same at 12 and 40 min after Na18F injection. Percentage errors in the estimation of the integrated value were 2.63% (n=12) for the arterial blood collected at 12 min and 4.14% (n=12) for the venous blood collected at 30 min. CONCLUSIONS: This simplified method is clinically applicable and would replace traditional methods that require multiple blood sampling.


Assuntos
Algoritmos , Doenças Ósseas/sangue , Doenças Ósseas/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador/métodos , Tomografia por Emissão de Pósitrons/métodos , Fluoreto de Sódio/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Técnicas de Diagnóstico por Radioisótopos , Feminino , Radioisótopos de Flúor/sangue , Radioisótopos de Flúor/farmacocinética , Humanos , Aumento da Imagem/métodos , Masculino , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos/sangue , Compostos Radiofarmacêuticos/farmacocinética , Reprodutibilidade dos Testes , Tamanho da Amostra , Sensibilidade e Especificidade , Fluoreto de Sódio/farmacocinética
10.
Ann Nucl Med ; 19(7): 549-55, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16363619

RESUMO

OBJECTIVE: Non-traumatic osteonecrosis of the femoral head (ONF) is considered to be a disease that occurs primarily due to ischemia of the femoral head, while its etiology and pathology are not fully understood. It is therefore necessary to identify the characteristics of the hemodynamics of the femoral head. In this study, the hemodynamics in the ilium and proximal regions of the femur, including the femoral head, was investigated using positron emission tomography (PET). METHODS: The subjects of this study consisted of 8 hip joints of four healthy male adults and 3 hip joints on the contralateral side of a femoral neck fracture, avulsion fracture of the greater trochanter and coxarthrosis (1 case each, all females) for a total of 11 hip joints of 7 subjects. The ages of the subjects ranged from 25 to 87 years (average age: 54 years). Blood flow was measured by means of the H215O dynamic study method and blood volume was measured by means of the 15O-labeled carbon monoxide bolus inhalation method. RESULTS: Blood flow was determined to be 9.1 +/- 4.8 ml/min/100 g in the ilium and among proximal regions of the femur (femoral head, neck and intertrochanteric region), 1.8 +/- 0.7 ml/min/100 g in the femoral head, 2.1 +/- 0.6 ml/min/100 g in the femoral neck, and 2.6 +/- 0.7 ml/min/100 g in the intertrochanteric region. In addition, blood volume was 4.7 +/- 1.3 ml/100 g in the ilium, and among proximal regions of the femur, 1.1 +/- 0.5 ml/100 g in the femoral head, 2.1 +/- 0.7 ml/100 g in the femoral neck, and 2.6 +/- 0.9 ml/100 g in the intertrochanteric region. The results showed that both blood flow and volume were lowest in the femoral head. Blood flow and volume were significantly lower in the proximal regions of the femur (femoral head, neck and intertrochanteric region) than in the ilium (p < 0.01). CONCLUSION: The present study demonstrated that the femoral head is in a hypoemic state as compared with other osseous tissue, indicating that even the slightest exacerbation of hemodynamics in the femoral head can trigger an ischemic condition culminating in ONF.


Assuntos
Velocidade do Fluxo Sanguíneo/fisiologia , Volume Sanguíneo/fisiologia , Cabeça do Fêmur/irrigação sanguínea , Cabeça do Fêmur/diagnóstico por imagem , Ílio/irrigação sanguínea , Ílio/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Determinação do Volume Sanguíneo/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência
11.
J Stroke Cerebrovasc Dis ; 14(6): 234-8, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-17904032

RESUMO

In symptomatic stenosis of the internal carotid artery (ICA), the predominant mechanism of ischemic event is considered thromboembolic. Carotid endarterectomy (CEA) removes the embolic source and is accepted as the major benefit from the surgery. Even in high-degree stenosis, hemodynamic compromise as a causal factor for cerebral ischemia remains controversial, however. We used positron emission tomography (PET) to evaluate possible hemodynamic and/or metabolic changes caused by a severe ICA stenosis and the subsequent changes after CEA. Subjects consisted of 10 patients with recent transient ischemic attack and/or minor stroke whose carotid stenosis exceeded 80% (mean, 92%). We measured regional cerebral blood flow (CBF), oxygen extraction fraction (OEF), oxygen metabolic rate (CMRO2), and regional cerebral blood volume (CBV) before and after the CEA. In addition, we calculated CBF/CBV value as an indicator of tissue perfusion reserve. We compared these PET values to those of 15 age-matched normal controls. Significant reductions in CBF, CBF/CBV, and CMRO2 values were observed in the hemisphere not only ipsilateral, but also contralateral to the stenosis. In 4 patients, an increase in OEF and decrease in CBF/CBV were also detected. These variables significantly recovered after CEA. High-degree carotid stenosis in the tested range reduces cerebral hemodynamic and metabolic reserve and forms a vulnerable environment in the brain. Successful CEA benefits not only by removing embolic source, but also by improving hemodynamic status, which may be seen in even the contralateral hemisphere.

12.
Appl Radiat Isot ; 106: 213-9, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26302661

RESUMO

To understand the mechanism of cell death induced by boron neutron capture reaction (BNCR), we performed proteome analyses of human squamous tumor SAS cells after BNCR. Cells were irradiated with thermal neutron beam at KUR after incubation under boronophenylalanine (BPA)(+) and BPA(-) conditions. BNCR mainly induced typical apoptosis in SAS cells 24h post-irradiation. Proteomic analysis in SAS cells suggested that proteins functioning in endoplasmic reticulum, DNA repair, and RNA processing showed dynamic changes at early phase after BNCR and could be involved in the regulation of cellular response to BNCR. We found that the BNCR induces fragments of endoplasmic reticulum-localized lymphoid-restricted protein (LRMP). The fragmentation of LRMP was also observed in the rat tumor graft model 20 hours after BNCT treatment carried out at the National Nuclear Center of the Republic of Kazakhstan. These data suggest that dynamic changes of LRMP could be involved during cellular response to BNCR.


Assuntos
Apoptose/efeitos da radiação , Terapia por Captura de Nêutron de Boro , Carcinoma de Células Escamosas/radioterapia , Neoplasias Bucais/radioterapia , Proteínas de Neoplasias/metabolismo , Proteômica , Carcinoma de Células Escamosas/metabolismo , Linhagem Celular Tumoral , Humanos , Neoplasias Bucais/metabolismo
13.
Appl Radiat Isot ; 61(5): 1069-73, 2004 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15308194

RESUMO

Recurrent head and neck malignancies (HNM) are often radio-/chemo-resistant and show extensive growth, necessitating a wide resection including surrounding tissues. To avoid severe impairment of oro-facial structures and functions, it is necessary to explore new treatments for HNM. Boron neutron capture therapy (BNCT) is tumor-cell targeted radiotherapy that has significant superiority over conventional radiotherapies in principle. We report here, first in the world, six patients with a recurrent HNM who have been treated with BNCT. The BNCT in combination with boronophenylalanine (BPA) and borocaptate sodium (BSH) was performed using the epithermal neutrons with Kyoto University Research Reactor (KUR). The results of BNCT were as follows: (1) (10)B concentration of tumor/normal tissue ratios (T/N ratio) of PET studies were SCC:1.8-4.4, sarcoma:3.1-4.0, parotid tumor:3.5. (2) Relative volume (%) of each tumor to the prior were 6-46%. (3) Remarkable reduction (46-100%) of huge tumor such as 40-675 cm(3) (average: 315 cm(3)), improvement of QOL and very mild side effects were recognized in all cases. These results indicate that BNCT represents a new and promising treatment approach even for a huge or far advanced HNM.


Assuntos
Terapia por Captura de Nêutron de Boro , Neoplasias de Cabeça e Pescoço/radioterapia , Recidiva Local de Neoplasia/radioterapia , Idoso , Carcinoma de Células Escamosas/radioterapia , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Neoplasias Parotídeas/radioterapia , Dosagem Radioterapêutica , Sarcoma/radioterapia
14.
Kaku Igaku ; 39(4): 543-8, 2002 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-12607243

RESUMO

Positron emission tomography (PET) radiotracers have very short physical half-lives. It is hard to complete a bacterial endotoxins test prior to release from medical institutes. For endotoxin quantitative determination, limulus amebocyte lysate (LAL) reagent and kinetic-turbidimetry system were previously developed. We investigated the possibility of a short time test by means of positively charged filters. As a result of this study, the effects of positively charged filters on endotoin removal were over 99.5% for [18F]FDG and [18F]NaF, which were contaminated with the indicated concentration of endotoxin. Combining this filter and the kinetic-turbidimetric method, it was possible to complete a bacterial endotoxins test in 5 min prior to the patient's administration. This test should be required prior to release for PET radiopharmaceutical quality control. It has been suggested that this combination is a good method for this purpose.


Assuntos
Contaminação de Medicamentos/prevenção & controle , Endotoxinas/isolamento & purificação , Filtros Microporos , Compostos Radiofarmacêuticos , Tomografia Computadorizada de Emissão , Endotoxinas/análise , Fluordesoxiglucose F18 , Concentração de Íons de Hidrogênio , Nefelometria e Turbidimetria , Controle de Qualidade , Fluoreto de Sódio
15.
Appl Radiat Isot ; 88: 104-8, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24690552

RESUMO

To understand the mechanism of tumor cell death induced by boron neutron capture therapy (BNCT) and to optimize BNCT condition, we used rat tumor graft models and histological and biochemical analyses were carried out focusing on DNA damage response. Rat lymphosarcoma cells were grafted subcutaneously into male Wister rats. The rats with developed tumors were then treated with neutron beam irradiation 45min after injection of 330mg/kg bodyweight boronophenylalanine ((10)BPA) (+BPA) or saline control (-BPA). BNCT was carried out in the National Nuclear Center of the Republic of Kazakhstan (neutron flux: 1×10(9)nvt/s, fluence: 6×10(11)nvt) with the presence of background γ-irradiation of 33Gy. 6 and 20h after BNCT treatment, tumors were resected, fixed and subjected to immunohistochemistry and biochemical analyses. Immunostaining of nuclei showed that double strand break (DSB) marker gamma H2AX staining was high in 20h/+BPA sample but not in 20h/-BPA samples. Poly(ADP-ribose), DSB and single strand break markers of DNA, also demonstrated this tendency. These two markers were observed at low levels in unirradiated tissues or 6h after BNCT either under -BPA and +BPA conditions. HMGB1 level increased in 6h/+BPA but not in 6h/-BPA or 20h/+BPA samples. The persistent staining of γH2AX and poly(ADP-ribose) in +BPA group suggests accumulated DSB damage after BNCT. The early HMGB1 upregulation and γH2AX and poly(ADP-ribose) observed later might be the markers for monitoring the DNA damage induced by BNCT.


Assuntos
Apoptose/genética , Terapia por Captura de Nêutron de Boro/métodos , Dano ao DNA/genética , Proteína HMGB1/genética , Histonas/genética , Linfoma não Hodgkin/genética , Linfoma não Hodgkin/patologia , Fosfoproteínas/genética , Animais , Apoptose/efeitos da radiação , Linhagem Celular Tumoral , Marcadores Genéticos/genética , Linfoma não Hodgkin/radioterapia , Masculino , Ratos , Ratos Wistar , Resultado do Tratamento
18.
Appl Radiat Isot ; 67(7-8 Suppl): S37-42, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19409799

RESUMO

It is necessary to explore new treatments for recurrent head and neck malignancies (HNM) to avoid severe impairment of oro-facial structures and functions. Boron neutron capture therapy (BNCT) is tumor-cell targeted radiotherapy that has significant superiority over conventional radiotherapies in principle. We have treated with BNCT 42 times for 26 patients (19 squamous cell carcinomas (SCC), 4 salivary gland carcinomas and 3 sarcomas) with a recurrent and far advanced HNM since 2001. Results of (1) (10)B concentration of tumor/normal tissue ratios (T/N ratio) of FBPA-PET studies were SCC: 1.8-5.7, sarcoma: 2.5-4.0, parotid tumor: 2.5-3.7. (2) Therapeutic effects were CR: 12 cases, PR: 10 cases, PD: 3 cases NE (not evaluated): 1 case. Response rate was 85%. (3) Improvement of QOL such as a relief of severe pain, bleeding, and exudates at the local lesion, improvement of PS, disappearance of ulceration, covered with normal skin and preserved oral and maxillofacial functions and tissues. (4) Survival periods after BNCT were 1-72 months (mean: 13.6 months). Six-year survival rate was 24% by Kaplan-Meier analysis. (5) Adverse-events were transient mucositis and alopecia in most of the cases; three osteomyelitis and one brain necrosis were recognized. These results indicate that BNCT represents a new and promising treatment approach for advanced HNM.


Assuntos
Terapia por Captura de Nêutron de Boro , Neoplasias de Cabeça e Pescoço/radioterapia , Recidiva Local de Neoplasia/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia por Captura de Nêutron de Boro/efeitos adversos , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/radioterapia , Feminino , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/mortalidade , Tomografia por Emissão de Pósitrons , Neoplasias das Glândulas Salivares/mortalidade , Neoplasias das Glândulas Salivares/radioterapia , Sarcoma/mortalidade , Sarcoma/radioterapia
19.
Appl Radiat Isot ; 67(7-8 Suppl): S15-8, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19398348

RESUMO

OBJECTIVE: Since 2002-2007, we applied boron neutron capture therapy (BNCT) to >50 cases of malignant gliomas (MGs) with epithermal neutron irradiations. Recently, we showed the early radiographical improvement of malignant glioma patients by our modified BNCT, with simultaneous use of BPA (borono-phenylalanine) and BSH (sodium borocaptate). In this time, we focused on the survival benefit from BNCT for the newly diagnosed glioblastoma patients. METHODS: BNCT group including 21 newly histological confirmed glioblastoma patients treated with surgical removal followed by BNCT in Osaka Medical College during 2002-2006 period. Ten patients were treated with BNCT only, and in the other 11 patients, 20-30 Gy fractionated external beam X-ray irradiation therapy (XRT) was performed after BNCT. No chemotherapy was administered until tumor progression was observed. RESULTS: Treatments were well tolerated. Any kind of acute systemic or local severe toxicity were not demonstrated. Mean over all survival of the patients treated by BNCT was 20.7 and the median was 15.6 months with 2-years survival of 25%. Stratification by RPA criteria showed 6, 6, 8 and 1 patients, respectively, in classes III-VI. Three patients out of six in class III and one out of eight in class V are alive at the end point of this study. All the patients in classes IV and VI died. Median survival time for the BNCT group compared to the RTOG database was as follows: 20.6 months vs. 17.9 months for class III; 16.9 months vs. 11.1 months for class IV; 13.2 months vs. 8.9 months for class V. CONCLUSION: The RTOG RPA prognostic criteria were helpful in establishing which class of glioma patients could potentially benefit from BNCT. BNCT showed a survival benefit in all of the RPA classes of the RTOG database not only for the good prognosis group.


Assuntos
Terapia por Captura de Nêutron de Boro/métodos , Neoplasias Encefálicas/radioterapia , Glioblastoma/radioterapia , Boroidretos/uso terapêutico , Compostos de Boro/uso terapêutico , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/cirurgia , Protocolos Clínicos , Terapia Combinada , Glioblastoma/mortalidade , Glioblastoma/cirurgia , Humanos , Japão/epidemiologia , Fenilalanina/análogos & derivados , Fenilalanina/uso terapêutico , Prognóstico , Radiossensibilizantes/uso terapêutico , Compostos de Sulfidrila/uso terapêutico , Taxa de Sobrevida
20.
J Neurooncol ; 89(2): 239-46, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18566749

RESUMO

Here we demonstrate that differentiation between glioblastoma (GB) tumor progression (TP) and radiation necrosis (RN) can be achieved with fluoride-labeled boronoalanine positron emission tomography (F-BPA-PET). F-BPA-PET images were obtained from histologically verified 38 GB, 8 complete RN, and 5 RN cases with partial residual tumors. The lesion/normal (L/N) ratios for these groups were 4.2 +/- 1.4, 1.5 +/- 0.3, and 2.0 +/- 0.3, respectively. Ten GB patients underwent F-BPA-PET twice (once before and once after radiation treatment) due to enlargement of the original lesion or the development of new lesions post radiation. The L/N ratios of ten original site lesions had decreased by the second PET, and these lesions were revealed to be RN. In contrast, the L/N ratios of two lesions distant from the original site increased, and these lesions were revealed as cases of TP. Repeat PET imaging was found to be useful for evaluating changes in GB-associated tumor activity with respect to the treatment received.


Assuntos
Boranos/metabolismo , Neoplasias Encefálicas/diagnóstico por imagem , Fluordesoxiglucose F18/metabolismo , Glioblastoma/diagnóstico por imagem , Fenilalanina/análogos & derivados , Tomografia por Emissão de Pósitrons , Neoplasias Encefálicas/patologia , Estudos de Avaliação como Assunto , Seguimentos , Glioblastoma/patologia , Humanos , Imageamento por Ressonância Magnética , Fenilalanina/metabolismo , Estudos Retrospectivos , Estatísticas não Paramétricas
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