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1.
Langmuir ; 36(24): 6668-6680, 2020 06 23.
Artículo en Inglés | MEDLINE | ID: mdl-32437159

RESUMEN

Inverted/reverse hexagonal (HII) phases are of special interest in several fields of research, including nanomedicine. We used molecular dynamics (MD) simulation to study HII systems composed of dioleoylphosphatidylethanolamine (DOPE) and palmitoyloleoylphosphatidylethanolamine (POPE) at several hydration levels and temperatures. The effect of the hydration level on several HII structural parameters, including deuterium order parameters, was investigated. We further used MD simulations to estimate the maximum hydrations of DOPE and POPE HII lattices at several given temperatures. Finally, the effect of acyl chain unsaturation degree on the HII structure was studied via comparing the DOPE with POPE HII systems. In addition to MD simulations, we used deuterium nuclear magnetic resonance (2H NMR) and small-angle X-ray scattering (SAXS) experiments to measure the DOPE acyl chain order parameters, lattice plane distances, and the water core radius in HII phase DOPE samples at several temperatures in the presence of excess water. Structural parameters calculated from MD simulations are in excellent agreement with the experimental data. Dehydration decreases the radius of the water core. An increase in hydration level slightly increased the deuterium order parameter of lipids acyl chains, whereas an increase in temperature decreased it. Lipid cylinders undulated along the cylinder axis as a function of hydration level. The maximum hydration levels of PE HII phases at different temperatures were successfully predicted by MD simulations based on a single experimental measurement for the lattice plane distance in the presence of excess water. An increase in temperature decreases the maximum hydration and consequently the radius of the water core and lattice plane distances. Finally, DOPE formed HII structures with a higher curvature compared to POPE, as expected. We propose a general protocol for constructing computational HII systems that correspond to the experimental systems. This protocol could be used to study HII systems composed of molecules other than the PE systems used here and to improve and validate force field parameters by using the target data in the HII phase.


Asunto(s)
Fosfatidilcolinas , Fosfatidiletanolaminas , Membrana Dobles de Lípidos , Espectroscopía de Resonancia Magnética , Dispersión del Ángulo Pequeño , Temperatura , Difracción de Rayos X
2.
Ann Surg Oncol ; 23(Suppl 5): 1021-1028, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-21547703

RESUMEN

BACKGROUND: The separate value of endoscopic ultrasonography (EUS), multidetector computed tomography (CT), and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in the optimal sequence in staging esophageal cancer has not been investigated adequately. METHODS: The staging records of 216 consecutive operable patients with esophageal cancer were reviewed blindly. Different staging strategies were analyzed, and the likelihood ratio (LR) of each module was calculated conditionally on individual patient characteristics. A logistic regression approach was used to determine the most favorable staging strategy. RESULTS: Initial EUS results were not significantly related to the LRs of initial CT and FDG-PET results. The positive LR (LR+) of EUS-fine-needle aspiration (FNA) was 4, irrespective of CT and FDG-PET outcomes. The LR+ of FDG-PET varied from 13 (negative CT) to 6 (positive CT). The LR+ of CT ranged from 3-4 (negative FDG-PET) to 2-3 (positive FDG-PET). Age, histology, and tumor length had no significant impact on the LRs of the three diagnostic tests. CONCLUSIONS: This study argues in favor of PET/CT rather than EUS as a predictor of curative resectability in esophageal cancer. EUS does not correspond with either CT or FDG-PET. LRs of FDG-PET were substantially different between subgroups of negative and positive CT results and vice versa.


Asunto(s)
Adenocarcinoma/diagnóstico por imagen , Carcinoma de Células Escamosas/diagnóstico por imagen , Endosonografía , Neoplasias Esofágicas/diagnóstico por imagen , Tomografía Computarizada Multidetector , Tomografía de Emisión de Positrones , Adenocarcinoma/secundario , Adenocarcinoma/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/secundario , Carcinoma de Células Escamosas/cirugía , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/cirugía , Esofagectomía , Femenino , Fluorodesoxiglucosa F18 , Humanos , Funciones de Verosimilitud , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/patología , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Selección de Paciente , Periodo Preoperatorio , Estudios Prospectivos , Radiofármacos
3.
Ann Surg Oncol ; 21(12): 3751-7, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24939624

RESUMEN

PURPOSE: To analyze the association between pretreatment 18-F-fluoro-deoxyglucose (FDG) uptake and characteristics of aggressive tumor biology in predicting outcome in esophageal cancer (EC). METHODS: Tumor FDG-uptake was measured by maximum standardized uptake values (SUVmax) in 47 patients undergoing esophagectomy with curative intent. ROC analyses were used to predict an optimal SUVmax cutoff for survival. Expression of hexokinase-II (HK-II), glucose transporter I (GLUT-I), hypoxia inducible factor-1α (HIF-Iα), vascular endothelial growth factor-C (VEGF-C), p53, and proliferative activity (Ki-67) were correlated with SUVmax values and clinicopathological characteristics. RESULTS: A SUVmax > 3.67 predicted a significantly lower disease-free survival (DFS) and distant recurrence-free survival (p = 0.022 and p = 0.005). High HK-II expression was correlated with reduced SUVmax values (p = 0.002) and was significantly higher in esophageal adenocarcinoma compared with squamous cell carcinoma (p = 0.005). Preoperative high FDG uptake in primary tumors was associated with nodal metastases (pN1; Spearman correlation 0.39, p = 0.01). We found no positive correlation between SUVmax and GLUT-1, HK-1, HIF-Iα 1, VEGF-C, p53, and Ki-67 expression. CONCLUSIONS: High preoperative FDG-uptake strongly predicts poor survival outcome and is associated with lymph node metastases in EC patients. HK-II expression was related to SUVmax and DFS.


Asunto(s)
Adenocarcinoma/secundario , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/secundario , Neoplasias Esofágicas/patología , Fluorodesoxiglucosa F18 , Radiofármacos , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/mortalidad , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Técnicas para Inmunoenzimas , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Tomografía de Emisión de Positrones , Pronóstico , Tasa de Supervivencia
4.
Q J Nucl Med Mol Imaging ; 56(5): 440-6, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23069923

RESUMEN

AIM: Radiotherapy following radical prostatectomy should be considered in men with high risk features who have a life expectancy of more than 10 years. So far no effect on prostate cancer specific survival has been proven by 3 randomized controlled trials (RCTs) on adjuvant radiotherapy. At present the optimal timing of radiotherapy is not defined. Identifying the site of recurrence is difficult at low PSA levels. [11C]choline PET-CT studies in biochemical recurrent prostate cancer after prostatectomy show a higher frequency of (false) negative cases compared to restaging after EBRT. It is uncertain if this reflects low volume of disease and/or low grade as biopsies fail to prove recurrent cancer in 50% of cases. We followed the clinical course of men with recurrent prostate cancer after radical prostatectomy and investigated treatment and survival. PET-CT data were correlated with clinical data, PSA kinetics and disease specific and overall survival. We also studied relative survival comparing an age matched group from the Central Dutch Statistical Office (CBS). METHODS: Sixty-four patients underwent [11C]choline PET-CT on PSA relapse. All patients were initially treated with radical prostatectomy and reached PSA nadir of <0.1 ng/mL. Recurrent disease was defined as PSA increase <0.2 ng/mL after nadir. Patients were either treated with watchful waiting, salvage radiotherapy and/or androgen deprivation therapy based on individual assessments by the treating urologists. Statistic: χ2, log-rank and Mann-Whitney-U tests were used to compare the [11C] choline PET/CT groups. RESULTS: The 64 patients had median PSA of 1.4 ng/mL. Median follow-up period of patients was 50 (6-124) months. Ten patients died during the course of follow-up of which 5 due to metastasized disease. No significant differences were seen in age, time to recurrence, total PSA at recurrence and PET-CT results. Patients with abnormal PET had higher PSAVel (median 3.09 ng/mL/yr versus 10.17, P=0.002) and shorter PSADT (med 4.83 months vs. 0.53, P=0.016). Median time to treatment was significantly lower in the PET-CT negative group. Age of patients at death from the whole group did not differ from the age of death in an age matched group. Disease specific survival was significantly higher in the PET-CT negative group (P=0.05). CONCLUSION: [11C]choline PET-CT showed that a negative PET/CT correlated with a higher disease specific survival and a lower treatment rate in men with a biochemical recurrence after radical prostatectomy. Overall survival of the total group was equal to the age matched cohort emphasizing the limited effect of a biochemical recurrent prostate cancer on overall survival. The optimum timing (adjuvant or early salvage) must be answered in running trials before adjuvant RT is used as standard of care.


Asunto(s)
Radioisótopos de Carbono , Colina , Prostatectomía , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/mortalidad , Anciano , Supervivencia sin Enfermedad , Humanos , Masculino , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/terapia , Cintigrafía , Tiempo de Tratamiento
5.
Q J Nucl Med Mol Imaging ; 56(2): 202-8, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22402821

RESUMEN

AIM: This study focuses on the potential role of [11C]choline positron emission tomography (PET) for the intraprostatic tumor characterization and localization in recurrent prostate cancer after EBRT. METHODS: This retrospective study was conducted in patients who were being followed up after EBRT for histological proven prostate cancer. We selected the patients with a local recurrence by [11C]choline PET/CT fusion. The results of PET were compared with the results of histology and with clinical follow-up. RESULTS: Forty-two patients with a local recurrence suggested by PET were included in this study. According to PET results: of the 42 patients, 15 (36%) had a focal recurrence, 27 (64%) showed a diffuse recurrence. The overall concordance of PET with histology concerning detection of recurrence was 76% (32 patients had positive PET results and positive biopsies). We confirmed the local recurrence as visualized by PET in 37/42 (88%) patients using a composite reference with histology and clinical follow up after local salvage treatment. The concordance of the intraprostatic distribution of the tumor with PET with histology from transrectal prostate biopsies (median biopsies 7, range 4-12) was 47% (7/15) in unilateral cases and 41% (11/27) in bilateral cases. No significant differences were seen between the 2 groups in serum PSA at time of PET (P=0.509) and SUV (P=0.739) using Student's t-test. CONCLUSION: Intraprostatic characterization of recurrent prostate cancer after EBRT with 11C-choline PET is feasible at present but shows a moderate concordance with routine transrectal prostate biopsies. The accuracy is too low for the routine use of this modality in the present scenario.


Asunto(s)
Colina , Recurrencia Local de Neoplasia/diagnóstico por imagen , Recurrencia Local de Neoplasia/prevención & control , Tomografía de Emisión de Positrones/métodos , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/radioterapia , Radioterapia Conformacional/métodos , Anciano , Radioisótopos de Carbono , Femenino , Humanos , Masculino , Persona de Mediana Edad , Radiofármacos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
6.
Ann Oncol ; 22(3): 559-566, 2011 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-20702788

RESUMEN

BACKGROUND: Both bevacizumab and erlotinib have clinical activity in non-small-cell lung cancer (NSCLC). Preclinical data suggest synergistic activity. PATIENTS AND METHODS: Chemonaive patients with stage IIIb or IV non-squamous NSCLC were treated with bevacizumab 15 mg/kg every 3 weeks and erlotinib 150 mg daily until progression. Primary end point was non-progression rate (NPR) at 6 weeks. Tumor response was measured with computed tomography, 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG-PET) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). KRAS and EGFR mutations were assessed in tumor samples. RESULTS: Forty-seven patients were included. Median follow-up was 15.2 months. NPR at 6 weeks was 75%. Median progression-free survival (PFS) was 3.8 [95% confidence interval (CI) 2.3-5.4] months and median overall survival (OS) was 6.9 (95% CI 5.5-8.4) months. Toxicity was mainly mild. The presence of KRAS (n = 10) or EGFR mutations (n = 5) did not influence outcome. After 3 weeks of treatment, >20% decrease in standard uptake value as measured with positron emission tomography predicted for longer PFS (9.7 versus 2.8 months; P = 0.01) and >40% decrease in K(trans) as assessed by DCE-MRI did not predict for longer PFS. CONCLUSIONS: First-line treatment with bevacizumab and erlotinib in stage IIIb/IV NSCLC resulted in an NPR of 75%. OS was however disappointing. Early response evaluation with FDG-PET is the best predictive test for PFS.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Adulto , Anciano , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales Humanizados , Bevacizumab , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Receptores ErbB/genética , Clorhidrato de Erlotinib , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Mutación , Metástasis de la Neoplasia , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas p21(ras) , Quinazolinas/administración & dosificación , Tomografía Computarizada de Emisión , Resultado del Tratamiento , Proteínas ras/genética
7.
Q J Nucl Med Mol Imaging ; 54(5): 543-52, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20927021

RESUMEN

Radiotherapy is one of the corner stone treatments for patients with prostate cancer. Especially for locally advanced tumors radiotherapy +/- adjuvant androgen deprivation treatment is standard of care. This brings up the need for accurate assessment of extra prostatic tumor growth and/or the presence of nodal metastases for selection of the optimal radiation dose and treatment volume. Morphological imaging like transrectal ultra sound, computed tomography (CT) and magnetic resonance imaging (MRI) are routinely used but are limited in their accuracy in detecting extra prostatic extension and nodal metastases. In this article we present a structured review of the literature on positron emission tomography (PET)/CT and radiotherapy in prostate cancer patients with emphasis on: 1) the pretreatment assessment of extra prostatic tumor extension, nodal and distant metastases; 2) the intraprostatic tumor characterization and radiotherapy treatment planning; and 3) treatment evaluation and the use of PET/CT in guidance of salvage treatment. PET/CT is not an appropriate imaging technique for accurate T-staging of prostate cancer prior to radiotherapy. Although macroscopic disease beyond the prostatic capsule and into the periprostatic fat or in seminal vesicle is often accurately detected, the microscopic extension of prostate cancer remains undetected. Choline PET/CT holds a great potential as a single step diagnostic procedure of lymph nodes and skeleton, which could facilitate radiotherapy treatment planning. At present the use of PET/CT for treatment planning in radiotherapy is still experimental. Choline PET based tumor delineation is not yet standardized and different segmentation-algorithms are under study. However, dose escalation using dose-painting is feasible with only limited increases of the doses to the bladder and rectum wall. PET/CT using either acetate or choline is able to detect recurrent prostate cancer after radiotherapy but stratification of patients for any local salvage treatment has not been addressed in the current literature.


Asunto(s)
Tomografía de Emisión de Positrones/métodos , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/radioterapia , Radioterapia/métodos , Tomografía Computarizada por Rayos X/métodos , Humanos , Masculino , Metástasis de la Neoplasia , Neoplasias de la Próstata/patología , Planificación de la Radioterapia Asistida por Computador
8.
Oral Oncol ; 45(8): 703-5, 2009 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-19147393

RESUMEN

Despite abundant literature on the use of PET in head and neck cancer, a little is known about the visualization of small laryngeal cancer. Moreover, most literature deals with the radiopharmaceutical (18)F-fludeoxyglucose (FDG), whereas only a few papers address the use of (11)C labeled amino acids. This study was performed to evaluate the feasibility of (11)C-labeled methionine in visualizing small laryngeal cancer. Ten patients with a de novo small laryngeal cancer (7 T1, 3 T2) underwent a MET PET at least 3 weeks after biopsy but prior to further treatment. Static scans were made in 'whole body' mode, covering the head from the external auditory meatus downwards to the whole thorax. The resulting images were judged by experienced specialists in nuclear medicine, who assessed the relative visibility of each tumor on a 3-point scale. Nine tumors were visualized (5 clearly, 4 moderately). One (T1) was not visualized. Small laryngeal cancer can be visualized with (11)C-methionine PET.


Asunto(s)
Neoplasias Laríngeas/diagnóstico por imagen , Metionina/análogos & derivados , Tomografía de Emisión de Positrones/métodos , Radiofármacos , Anciano , Anciano de 80 o más Años , Estudios de Factibilidad , Femenino , Glotis/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estudios Prospectivos
9.
Acta Neurochir (Wien) ; 150(4): 345-9, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18278573

RESUMEN

BACKGROUND: We studied the use of (201)Thallium SPECT and L-[1-(11)C]-tyrosine PET in patients with a primary glioblastoma multiforme treated with (192)Ir brachytherapy after surgery and external beam radiation therapy. We hypothesised that the patients most likely to benefit from further surgery after deterioration would be those with radiation necrosis and would be recognised by a negative emission tomography scan. METHODS: Twenty-one patients underwent (201)Thallium SPECT performed before brachytherapy, and this was repeated in 19 patients when recurrence was suspected. Nine patients also underwent a PET scan at the same time. Nine patients underwent a second operation. FINDINGS: SPECT and PET were highly concordant concerning the prediction of radionecrosis and/or tumour recurrence. Repeat surgery did not lead to a significant increase in survival. There was no significant association between the duration of survival and tumour-to-background ratio but the number studied was small. Both SPECT and PET showed highly active lesions, which were proved to be recurrent tumour by clinical and histological follow-up. CONCLUSION: Although PET and SPECT are both highly sensitive in detecting active tumour tissue, emission tomography was not clinically valuable in the investigation of patients with a primary glioblastoma treated with brachytherapy.


Asunto(s)
Braquiterapia , Neoplasias Encefálicas/radioterapia , Irradiación Craneana , Glioblastoma/radioterapia , Radioisótopos de Iridio/uso terapéutico , Recurrencia Local de Neoplasia/diagnóstico por imagen , Complicaciones Posoperatorias/diagnóstico por imagen , Tomografía Computarizada de Emisión de Fotón Único , Adulto , Anciano , Encéfalo/diagnóstico por imagen , Encéfalo/efectos de la radiación , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/cirugía , Radioisótopos de Carbono , Terapia Combinada , Diagnóstico Diferencial , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Glioblastoma/diagnóstico por imagen , Glioblastoma/mortalidad , Glioblastoma/cirugía , Humanos , Radioisótopos de Iridio/efectos adversos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/cirugía , Tomografía de Emisión de Positrones , Complicaciones Posoperatorias/cirugía , Traumatismos por Radiación/diagnóstico por imagen , Radioterapia Adyuvante , Reoperación , Sensibilidad y Especificidad , Radioisótopos de Talio , Tirosina
10.
Clin Neurol Neurosurg ; 110(2): 182-5, 2008 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-17964071

RESUMEN

In a patient with a refractory generalized convulsive status epilepticus, the ictal distribution of regional cerebral glucose was assessed with positron emission tomography (PET). Synchronized seizure activity in the EEG was associated with bilateral metabolic activation of medial sensorimotor regions, anterior cingulate cortex, striatum and thalamus. This pattern with focal cortical activation supports the concept that a cortical focus may drive epilepsy, while the thalamus mediates synchronization of neuronal activity as reflected in the EEG.


Asunto(s)
Corteza Cerebral/metabolismo , Estado Epiléptico/diagnóstico por imagen , Estado Epiléptico/metabolismo , Tálamo/metabolismo , Adulto , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/fisiopatología , Electroencefalografía , Femenino , Humanos , Tomografía de Emisión de Positrones , Estado Epiléptico/fisiopatología , Tálamo/diagnóstico por imagen , Tálamo/fisiopatología
12.
Psychopharmacology (Berl) ; 183(3): 322-30, 2005 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-16220327

RESUMEN

RATIONALE: The dopaminergic system has been implicated in the pathogenesis and treatment of a variety of neuropsychiatric disorders. It has been shown that information on endogenous dopamine (DA) release can be obtained noninvasively by combining positron emission tomography with a dopaminergic challenge. This approach is based on the assumption that an injected radiolabeled ligand competes with the neurotransmitter for the same receptor. Increases in DA release will therefore result in a decreased binding of the radioligand. OBJECTIVES: We investigated the effect of the DA reuptake blocker methylphenidate (MP) on the binding of the D(2) receptor ligand [(11)C]-raclopride (RAC). METHODS: The effect of a 0.25 mg/kg intravenous dose of MP was studied in six healthy volunteers. RAC was administered as a bolus followed by constant infusion, and subjective effects were assessed using verbal rating scales. RESULTS: Control scans without MP administration showed that the mean RAC binding reached stable values approximately 30 min after start of the infusion. MP administration induced a 24% decrease in RAC binding in the total striatum. Correlations were found between the MP-induced change in euphoria and the percent change in binding potential (DeltaBP) in the dorsal striatum and between baseline anxiety and DeltaBP in the dorsal and middle striatum. We also found a negative correlation between baseline BP in the dorsal striatum and change in euphoria. CONCLUSIONS: Our results comply with previous findings, indicating the feasibility of the bolus infusion design combined with a relatively low MP dose to study dopaminergic (dys)function.


Asunto(s)
Radioisótopos de Carbono , Metilfenidato/farmacología , Racloprida/metabolismo , Receptores de Dopamina D2/efectos de los fármacos , Adolescente , Adulto , Presión Sanguínea/efectos de los fármacos , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Masculino , Tomografía de Emisión de Positrones , Receptores de Dopamina D2/análisis
13.
Neurology ; 65(6): 941-3, 2005 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-16186542
14.
J Neurol Neurosurg Psychiatry ; 76(9): 1217-21, 2005 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-16107354

RESUMEN

OBJECTIVES: Glutamate mediated excitotoxicity of the hyperactive subthalamic nucleus (STN) has been reported to contribute to nigral degeneration in Parkinson's disease (PD). Deep brain stimulation of the STN (STN DBS), in its role as a highly effective treatment of severe PD motor complications, has been thought to inhibit STN hyperactivity and therefore decrease progression of PD. METHODS: In a prospective two centre study, disease progression was determined by means of serial (18)F-fluorodopa (F-dopa) positron emission tomography (PET) in 30 patients with successful STN DBS over the first 16 (SD 6) months after surgery. RESULTS: Depending on the method of PET data analysis used in the two centres, annual progression rates relative to baseline were 9.5-12.4% in the caudate and 10.7-12.9% in the putamen. CONCLUSIONS: This functional imaging study is the first to demonstrate a continuous decline of dopaminergic function in patients with advanced PD under clinically effective bilateral STN stimulation. The rates of progression in patients with STN DBS were within the range of previously reported data from longitudinal imaging studies in PD. Therefore this study could not confirm the neuroprotective properties of DBS in the STN target.


Asunto(s)
Estimulación Encefálica Profunda , Enfermedad de Parkinson/patología , Enfermedad de Parkinson/terapia , Núcleo Subtalámico/fisiología , Anciano , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tomografía de Emisión de Positrones , Estudios Prospectivos , Receptores Dopaminérgicos/fisiología
15.
J Neural Transm (Vienna) ; 111(12): 1575-81, 2004 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-15565491

RESUMEN

Mutations in the DJ-1 gene lead to autosomal recessive early-onset parkinsonism. We performed F-DOPA and FDG PET neuroimaging in two parkinsonism patients homozygous for DJ-1 mutations, three relatives heterozygous for a DJ-1 mutation and one non-carrier, all from the originally described kindred from The Netherlands. Their characteristics were compared to those of typical Parkinson's disease patients and healthy controls. Both parkinsonism patients had reduced F-DOPA uptake concordant with typical Parkinson's disease. In the, clinically unaffected, heterozygous relatives, F-DOPA metabolism was unremarkable, thus not suggesting a dosage effect of the DJ-1 gene.


Asunto(s)
Encéfalo/diagnóstico por imagen , Proteínas Oncogénicas/genética , Trastornos Parkinsonianos/diagnóstico por imagen , Humanos , Péptidos y Proteínas de Señalización Intracelular , Mutación , Tomografía de Emisión de Positrones , Proteína Desglicasa DJ-1
16.
J Clin Oncol ; 22(18): 3805-12, 2004 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-15365078

RESUMEN

PURPOSE: Despite the increasing number of publications concerning (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) for staging of esophageal cancer and the increasing availability of this novel diagnostic modality, its exact role in preoperative staging of these tumors is still unknown. The aim of this study was to systematically review the literature regarding the diagnostic performance of FDG-PET in preoperative staging of patients with esophageal cancer, and to calculate summary estimates of its sensitivity and specificity. METHODS: The databases of PubMed, Embase, and Cochrane were searched for relevant studies. Two reviewers independently assessed the methodological quality of each study. A meta-analysis of the reported sensitivity and specificity of each study was performed. RESULTS: Twelve studies met the inclusion criteria. The studies had several design deficiencies. Pooled sensitivity and specificity for the detection of locoregional metastases were 0.51 (95% CI, 0.34 to 0.69) and 0.84 (95% CI, 0.76 to 0.91), respectively. For distant metastases, pooled sensitivity and specificity were 0.67 (95% CI, 0.58 to 0.76) and 0.97 (95% CI, 0.90 to 1.0), respectively. CONCLUSION: FDG-PET showed moderate sensitivity and specificity for the detection of locoregional metastases, and reasonable sensitivity and specificity in detection of distant lymphatic and hematogenous metastases.


Asunto(s)
Neoplasias Esofágicas/diagnóstico por imagen , Neoplasias Esofágicas/patología , Fluorodesoxiglucosa F18 , Estadificación de Neoplasias/métodos , Radiofármacos , Tomografía Computarizada de Emisión , Ensayos Clínicos como Asunto , Humanos , Sensibilidad y Especificidad
17.
Thorax ; 59(7): 596-601, 2004 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-15223868

RESUMEN

BACKGROUND: Positron emission tomography (PET) is accurate for mediastinal staging of lung cancer but has a moderate positive predictive value, necessitating pathological verification. Endoscopic ultrasonography with fine needle aspiration (EUS-FNA) is a technique for tissue verification of mediastinal and upper retroperitoneal abnormalities. The use of EUS-FNA may decrease the number of surgical procedures and thereby staging costs. METHODS: EUS-FNA was used prospectively for the cytological assessment of mediastinal and/or upper retroperitoneal PET hot spots in patients with suspected lung cancer. Only if EUS-FNA was positive for malignancy was subsequent mediastinoscopy or exploratory thoracotomy cancelled. The cost effectiveness of EUS-FNA was determined. RESULTS: Of 488 consecutive patients with suspected lung cancer, 81 were enrolled with mediastinal and/or upper retroperitoneal PET hot spots. EUS-FNA was positive in 50 (62%) patients, negative in six, and inconclusive in 25. Of the 31 negative or inconclusive patients, 26 underwent surgical staging (resulting in 14 patients with and 12 without mediastinal malignancy), while five patients had mediastinal metastases during follow up. No EUS-FNA related morbidity or mortality was encountered. The accuracy of the decision to proceed to surgery (or not) on the basis of EUS-FNA was 77% (95% CI 68 to 86). EUS-FNA detected more mediastinal abnormalities than PET except for the upper mediastinal region. Addition of EUS-FNA to conventional lung cancer staging reduced staging costs by 40% per patient, mainly due to a decrease in surgical staging procedures. CONCLUSION: EUS-FNA can replace more than half of the surgical staging procedures in lung cancer patients with mediastinal and/or upper retroperitoneal PET hot spots, thereby saving 40% of staging costs.


Asunto(s)
Biopsia con Aguja Fina/métodos , Endosonografía/métodos , Neoplasias Pulmonares/patología , Pulmón/patología , Estadificación de Neoplasias/métodos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Metástasis Linfática/diagnóstico por imagen , Metástasis Linfática/patología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Tomografía Computarizada de Emisión , Ultrasonografía Intervencional
18.
Eur Urol ; 44(1): 32-8; discussion 38-9, 2003 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-12814672

RESUMEN

RATIONALE: The evaluation of the efficacy of the treatment of men with prostate cancer is largely based on post treatment levels of PSA. An increase in PSA or biochemical recurrence is the first sign of recurrent disease and precedes a clinically detectable recurrence by months to years. Digital rectal examination and conventional imaging techniques are not sensitive to detect a local recurrence. A metabolic imaging technique, which is not dependent on anatomical distortions, could be of use. In this study we investigated 11C-choline positron emission tomography (PET) for the evaluation after treatment of localized prostate cancer. METHODS: Thirty-six patients with localized prostate cancer, treated by either radical prostatectomy (n=20) or by external beam radiotherapy (n=16) were studied with 11C-choline PET. The results of PET were compared with the results of histology and with clinical follow up. RESULTS: Fourteen patients had no biochemical failure after therapy. 11C-choline PET was true negative in 14/14 patients. Twenty-two patients had a biochemical failure. In the radical prostatectomy patients 11C-choline PET was true positive in 5/13 (38%) cases. In the external beam radiotherapy patients 11C-choline PET was true positive in 7/9 (78%). The recurrent tumor was confirmed by biopsy or by bone scan in eleven of the twelve true positive patients. In ten patients with a negative 11C-choline PET scan, no recurrent tumor could be proven yet clinically, by biopsy or during follow up. CONCLUSION: 11C-choline PET is a feasible technique for evaluation of treatment for localized prostate cancer. The site of recurrence was detected correctly in 78% of the patients after external beam radiotherapy compared to 38% of the patients after radical prostatectomy. No positive PET scans were observed sofar in patients with a serum PSA <5ng/ml. Confirmatory studies and longer follow up are needed to determine the efficacy of 11C-choline PET compared to other imaging techniques.


Asunto(s)
Recurrencia Local de Neoplasia/diagnóstico por imagen , Recurrencia Local de Neoplasia/patología , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Tomografía Computarizada de Emisión/métodos , Cuidados Posteriores , Anciano , Anciano de 80 o más Años , Biopsia con Aguja , Braquiterapia/métodos , Colina , Estudios de Cohortes , Humanos , Masculino , Persona de Mediana Edad , Monitoreo Fisiológico/métodos , Estadificación de Neoplasias , Pronóstico , Prostatectomía/métodos , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/cirugía , Radiofármacos , Sensibilidad y Especificidad
19.
J Neurol Sci ; 210(1-2): 23-30, 2003 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-12736083

RESUMEN

Positron emission tomography (PET) was used for the study of regional cerebral perfusion and metabolism in eight patients with severe post-hypoxic encephalopathy, caused by cardiac arrest and resulting in a coma lasting for at least 24 h. Using this method, we aimed to identify regional vulnerability, which was hypothesized to provide (i) insight in pathogenic mechanisms and (ii) early prognostic parameters. On day 1 post-resuscitation, 18-Fluor deoxyglucose ([F18]-FDG) indicated a marked decrease of cerebral metabolic activity. Gray matter glucose consumption was 54% of normal values, whereas white matter uptake was 70% of normal. Regional differences followed a pattern of neuronal density rather than specific patterns of functionally or biochemically defined regions or of vascular territories. In contrast to [F18]-FDG, the distribution of 15-oxygen labeled water ([O-15]-water) showed a better demarcation between gray and white matter, whereas focal deficit was not observed. In some patients, hyperperfusion relative to regional glucose consumption was observed in the occipital poles and basal ganglia. This suggests loss of vascular tone, i.e. vascular paralysis, in the basilar artery territory. CT and MRI scanning did not show any major change with respect to the hypoxic injury. In the small group studied, all patients had a poor outcome. The comparison between survivors and nonsurvivors did not reveal obvious differences in PET data, suggesting that this technique does not provide major prognostic clues adding to the prognostic information derived from serial neurological assessment in the restricted patient group characterized by prolonged coma.


Asunto(s)
Encéfalo/metabolismo , Hipoxia Encefálica/metabolismo , Resucitación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Encéfalo/anatomía & histología , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Mapeo Encefálico , Quimioterapia del Cáncer por Perfusión Regional/métodos , Economía , Femenino , Fluorodesoxiglucosa F18/metabolismo , Glucosa/metabolismo , Paro Cardíaco/metabolismo , Humanos , Hipoxia Encefálica/diagnóstico por imagen , Hipoxia Encefálica/etiología , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Consumo de Oxígeno , Estudios Prospectivos , Distribución Tisular , Tomografía Computarizada de Emisión
20.
Eur Urol ; 42(1): 18-23, 2002 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-12121724

RESUMEN

BACKGROUND AND OBJECTIVE: Visualization of prostate cancer with positron emission tomography (PET) using 2-[18F]-2-deoxy-D-glucose (FDG) as radiopharmaceutical is limited by the low uptake of FDG in the tumor and by radioactivity excreted into the bladder. More specific PET radiopharmaceuticals would be welcome. Carbon-11 labeled choline (CHOL) is a new radiopharmaceutical potentially useful for tumor imaging as it is incorporated in the cell membranes as phosphatidylcholine. We prospectively studied the visualization of prostate cancer using CHOL PET. METHODS: A total of 25 consecutive patients with histologically proven prostate cancer and five patients with a benign prostate were included. PET images were performed with an ECAT HR(+) using 400MBq CHOL. Data acquisition was started at 5 minutes post-injection. Attenuation-corrected images were evaluated visually. Standardized uptake values (SUV) were calculated of the normal prostate gland and of the prostate tumor tissue. RESULTS: The normal prostate was visualized with a mean SUV of 2.3 (range 1.3-3.2). The primary tumor could be visualized with a mean SUV of 5.0 (range 2.4-9.5). Lymph node metastases >5mm could be identified. Non-specific uptake of CHOL was noticed in the intestines. Little to no radioactivity in the bladder was observed. CONCLUSION: Carbon-11-choline is avidly taken up in prostate cancer, both primary tumor and lymph node metastases, in the virtual absence of urinary radioactivity. These results confirm the early results obtained by others and permit further clinical research on the value of CHOL PET as a metabolic imaging technique in areas where conventional imaging have a limited sensitivity.


Asunto(s)
Radioisótopos de Carbono , Colina , Neoplasias de la Próstata/diagnóstico por imagen , Tomografía Computarizada de Emisión , Anciano , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Persona de Mediana Edad , Radiofármacos
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