RESUMO
PURPOSE: To determine the metabolic profiles of the translocator protein ligands PBR102 and PBR111 in rat and human microsomes and compare their in vivo binding and metabolite uptake in the brain of non-human primates (Papio hamadryas) using PET-CT. METHODS: In vitro metabolic profiles of PBR102 and PBR111 in rat and human liver microsomes were assessed by liquid chromatography-tandem mass spectrometry. [18F]PBR102 and [18F]PBR111 were prepared by nucleophilic substitution of their corresponding p-toluenesulfonyl precursors with [18F]fluoride. List mode PET-CT brain imaging with arterial blood sampling was performed in non-human primates. Blood plasma measurements and metabolite analysis, using solid-phase extraction, provided the metabolite profile and metabolite-corrected input functions for kinetic model fitting. Blocking and displacement PET-CT scans, using PK11195, were performed. RESULTS: Microsomal analyses identified the O-de-alkylated, hydroxylated and N-de-ethyl derivatives of PBR102 and PBR111 as the main metabolites. The O-de-alkylated compounds were the major metabolites in both species; human liver microsomes were less active than those from rat. Metabolic profiles in vivo in non-human primates and previously published rat experiments were consistent with the microsomal results. PET-CT studies showed that K1 was similar for baseline and blocking studies for both radiotracers; VT was reduced during the blocking study, suggesting low non-specific binding and lack of appreciable metabolite uptake in the brain. CONCLUSIONS: [18F]PBR102 and [18F]PBR111 have distinct metabolic profiles in rat and non-human primates. Radiometabolites contributed to non-specific binding and confounded in vivo brain analysis of [18F]PBR102 in rodents; the impact in primates was less pronounced. Both [18F]PBR102 and [18F]PBR111 are suitable for PET imaging of TSPO in vivo. In vitro metabolite studies can be used to predict in vivo radioligand metabolism and can assist in the design and development of better radioligands.
Assuntos
Encéfalo/metabolismo , Imidazóis/farmacocinética , Imagem Molecular/métodos , Tomografia por Emissão de Pósitrons/métodos , Piridinas/farmacocinética , Receptores de GABA/metabolismo , Animais , Encéfalo/diagnóstico por imagem , Avaliação Pré-Clínica de Medicamentos/métodos , Humanos , Marcação por Isótopo/métodos , Ligantes , Masculino , Taxa de Depuração Metabólica , Especificidade de Órgãos , Papio , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/farmacocinética , Ratos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Especificidade da Espécie , Distribuição TecidualRESUMO
We propose a novel joint probabilistic model that correlates a new probabilistic shape model with the corresponding global intensity distribution to segment multiple abdominal organs simultaneously. Our probabilistic shape model estimates the probability of an individual voxel belonging to the estimated shape of the object. The probability density of the estimated shape is derived from a combination of the shape variations of target class and the observed shape information. To better capture the shape variations, we used probabilistic principle component analysis optimized by expectation maximization to capture the shape variations and reduce computational complexity. The maximum a posteriori estimation was optimized by the iterated conditional mode-expectation maximization. We used 72 training datasets including low- and high-contrast CT images to construct the shape models for the liver, spleen and both kidneys. We evaluated our algorithm on 40 test datasets that were grouped into normal (34 normal cases) and pathologic (6 datasets) classes. The testing datasets were from different databases and manual segmentation was performed by different clinicians. We measured the volumetric overlap percentage error, relative volume difference, average square symmetric surface distance, false positive rate and false negative rate and our method achieved accurate and robust segmentation for multiple abdominal organs simultaneously.
Assuntos
Tomografia Computadorizada de Feixe Cônico/métodos , Processamento de Imagem Assistida por Computador/métodos , Modelos Estatísticos , Radiografia Abdominal/métodos , Algoritmos , Bases de Dados Factuais , Humanos , Fígado/anatomia & histologia , Análise de Componente Principal , Reprodutibilidade dos TestesRESUMO
Upgrades and optimisation achieved 160 µA total target current operation of a GE PETtrace cyclotron in dual target mode for the routine production of [(18)F]FDG for >2 years. Approximately 900 GBq of (18)F(-) and >500 GBq of [(18)F]FDG can be produced routinely in a single production run, meeting the routine [(18)F]FDG requirements with our customer base and achieving economies of scale. Production of >1 TBq of (18)F(-) in a single run was achieved. Reliability, saturation and synthesis yields were not adversely affected.
Assuntos
Ciclotrons , Fluordesoxiglucose F18/síntese química , Marcação por Isótopo/instrumentação , Tomografia por Emissão de Pósitrons/instrumentação , Compostos Radiofarmacêuticos/síntese química , Desenho de Equipamento , Análise de Falha de Equipamento , Fluordesoxiglucose F18/efeitos da radiação , Teste de Materiais , Doses de RadiaçãoRESUMO
Susac's syndrome is the clinical triad of encephalopathy, branch retinal artery occlusions and sensorineural hearing loss (Susac 1994) [1]. It occurs predominantly in young females and is believed to be an immune-mediated endotheliopathy of small vessels of the brain, retina and cochlea (Neumayer et al. 2009) [2]. Early, aggressive, and sustained immunosuppressive therapy has been recommended for Susac's syndrome and anecdotal evidence has suggested a therapeutic role for monoclonal antibodies (Rennebohm et al. 2008, Lee and Amezcua 2009) [3,4]. We report a case of Susac's syndrome in which the patient improved immediately after tumour necrosis factor (TNF) inhibition with the monoclonal antibody, infliximab.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Síndrome de Susac/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Anti-Inflamatórios/uso terapêutico , Azatioprina/uso terapêutico , Encéfalo/patologia , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/psicologia , Ciclofosfamida/uso terapêutico , Epilepsia Generalizada/etiologia , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Imunossupressores/uso terapêutico , Infliximab , Imageamento por Ressonância Magnética , Testes Neuropsicológicos , Prednisona/uso terapêutico , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Convulsões/etiologia , Síndrome de Susac/psicologia , Adulto JovemRESUMO
OBJECTIVE: To assess the impact of FDG PET-CT on the management of patients with suspected recurrent ovarian cancer and to determine the incremental information provided by PET-CT. METHODS: This was a prospective, multi-centre, cohort study. Ninety women (mean age 59.9 years; age range 35-85 years) with a previous history of treated epithelial ovarian carcinoma and suspected recurrence based on elevated CA-125, anatomical imaging or clinical symptoms were studied with FDG PET-CT across two States. Referring doctors were asked to specify a management plan pre-PET, if management was altered after PET-CT and, the impact (rated - none, low, medium, high) of PET-CT on patient management. The pre-PET management plan could include radiotherapy, chemotherapy, surgery, and 'other' including observation. Patients were followed at 6 and 12 months and clinical status, evidence of recurrence and progression were recorded. RESULTS: Patients were referred by 34 individual specialists. At least 168 additional sites of disease in 61 patients (68%), not identified by conventional imaging were identified by PET-CT. In 77% the additional lesions were located below the diaphragm and most were nodal or peritoneal. PET-CT affected management in 60% (49% high, 11% medium impact). Patients where more disease was detected with PET-CT were more likely to progress in the following 12 months. CONCLUSIONS: For women with previously treated ovarian carcinoma with recurrent disease, PET-CT can: a) alter management in close to 60% of patients, b) detect more sites of disease than abdominal and pelvic CT, c) is superior in the detection of nodal, peritoneal and subcapsular liver disease and d) offers the opportunity for technology replacement in this setting.
Assuntos
Fluordesoxiglucose F18 , Recidiva Local de Neoplasia/diagnóstico por imagem , Neoplasias Ovarianas/diagnóstico por imagem , Compostos Radiofarmacêuticos , Adulto , Idoso , Idoso de 80 Anos ou mais , Austrália , Feminino , Radioisótopos de Flúor , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/terapia , Neoplasias Ovarianas/terapia , Tomografia por Emissão de Pósitrons/métodos , Estudos Prospectivos , Tomografia Computadorizada por Raios X/métodosRESUMO
We present the staging fluorodeoxyglucose (FDG) positron emission tomography (PET-CT) findings in a patient with a functional urinary bladder paraganglioma. The PET-CT scan showed markedly increased FDG uptake into bilateral pelvic nodes that was consistent with regional nodal involvement. These findings were confirmed on histopathology. At present, there are no reports of PET-CT findings in urinary bladder paragangliomas.
Assuntos
Fluordesoxiglucose F18 , Paraganglioma/diagnóstico , Tomografia por Emissão de Pósitrons/métodos , Tomografia Computadorizada por Raios X/métodos , Neoplasias da Bexiga Urinária/diagnóstico , Adolescente , Humanos , Masculino , Compostos Radiofarmacêuticos , Técnica de SubtraçãoRESUMO
We present the FDG PET-CT findings in a patient with persistent pain 7 weeks after a nephrectomy and lymph node dissection for a sarcomatoid renal cell carcinoma. Although conventional imaging was unable to detect evidence of metastatic spread outside the para-aortic nodes, a PET-CT scan showed unexpected extensive dissemination. Currently, there are no reports in the literature of the PET-CT findings in sarcomatoid renal cell carcinomas.
Assuntos
Carcinoma de Células Renais/diagnóstico por imagem , Neoplasias Renais/diagnóstico por imagem , Sarcoma/diagnóstico por imagem , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , Fluordesoxiglucose F18 , Humanos , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Sarcoma/patologia , Sarcoma/cirurgia , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: Positron emission tomography with [(18)F]fluorodeoxyglucose (FDG-PET) is of proven value in the detection of metastases in patients with cutaneous melanoma. However, little is known about its value in uveal melanoma (UM). In this study the results of FDG-PET in patients with UM were evaluated. METHODS: Patients with UM recorded in the Sydney Melanoma Unit database who had been assessed with FDG-PET were selected. Comparative data (imaging or histopathology) providing information about metastatic disease were obtained within 14 weeks of the FDG-PET study and compared with the FDG-PET result. Sensitivity, specificity, accuracy, and positive and negative predictive values for the detection of liver metastases (LMs) by FDG-PET were calculated. RESULTS: FDG-PET was performed in 22 patients with UM between April 1993 and March 2003. The presence of at least one focus of metastatic melanoma was confirmed in 14 of 18 patients with positive FDG-PET, and three of four negative FDG-PET studies were confirmed. LMs were demonstrated by FDG-PET in 17 patients. In 15 of these patients this finding was confirmed with anatomical imaging. In two patients LMs indicated by FDG-PET initially appeared to be false positive, but in one of them the diagnosis was confirmed after longer follow-up. Seven of the confirmed lesions were isolated LMs. For LMs FDG-PET showed sensitivity, specificity and accuracy of 100%, 67% and 90% respectively, a positive predictive value of 88% and a negative predictive value of 100%. CONCLUSION: FDG-PET is a valuable investigation for the detection of LMs in UM patients. It appears to be particularly useful in the detection of isolated LMs that are potentially resectable.
Assuntos
Melanoma/diagnóstico por imagem , Melanoma/secundário , Tomografia por Emissão de Pósitrons , Neoplasias Uveais/patologia , Adulto , Idoso , Feminino , Fluordesoxiglucose F18 , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Valor Preditivo dos Testes , Compostos Radiofarmacêuticos , Sensibilidade e EspecificidadeRESUMO
AIM: Positron emission tomography (PET) using (18)F-fluorodeoxyglucose can detect early or small metastatic deposits of melanoma and guide subsequent correlative anatomical imaging and treatment. The aim of this study was to assess the value of PET in demonstrating spinal cord compression by otherwise unsuspected metastatic disease. METHODS: Reports of 1365 PET studies performed on patients with melanoma were reviewed. Fifty patients considered to be at risk of spinal cord compression on the basis of PET were identified and 35 patients were analysed. Magnetic resonance imaging and computed tomography were used to confirm or refute the diagnosis. The symptoms and signs at the time of PET and follow-up status were compared between patients with and without confirmed spinal cord compression. RESULTS: In nine patients (26%) compression of the spinal cord or adjacent neurological structures was confirmed and eight of these patients had immediate treatment. Survival was poor in both patient groups, but three patients with confirmed compression maintained good neurological functional status following treatment. CONCLUSION: PET can detect imminent, unsuspected spinal cord compression in patients with metastatic melanoma. Immediate anatomical imaging of the spine is recommended in patients who have evidence of spinal cord compression on PET.
Assuntos
Fluordesoxiglucose F18 , Melanoma/diagnóstico , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Compressão da Medula Espinal/diagnóstico , Neoplasias da Medula Espinal/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Vértebras Cervicais/patologia , Vértebras Cervicais/efeitos da radiação , Vértebras Cervicais/cirurgia , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Melanoma/terapia , Pessoa de Meia-Idade , Radioterapia , Compressão da Medula Espinal/terapia , Neoplasias da Medula Espinal/terapia , Procedimentos Cirúrgicos Operatórios , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
To develop a suitable single photon emission computed tomography (SPECT) radioligand for neuronal nicotinic acetylcholine receptors (nAChRs) that displays faster in vivo kinetics than 5-[123I]iodo-A-85380, we synthesised the radioiodinated analogue of A-84543. 5-[123I]Iodo-A-84543 was prepared by electrophilic iododestannylation in a modest yield of 23%. In the baboon brain, 5-[123I]iodo-A-85380 displayed a profile consistent with the known distribution of nAChRs, however, 5-[123I]iodo-A-84543 displayed a homogenous uptake with no preferential localisation in regions known to contain nAChRs. To examine the effect of halogen substitution on the 3-pyridyl ether, A-84543, the 5-chloro, 5-bromo and 5-iodo analogues were synthesised and evaluated with respect to nAChR binding. In vitro binding data revealed that halogen substitution at the 5-position of A-84543 was not well tolerated with an increase in halogen size resulting in lower binding towards nAChRs. The 5-chloro analogue 4 displayed highest affinity, Ki =1.3 nM, compared to the 5-bromo and 5-iodo compounds, 5 Ki =3.3 nM and 3 Ki =40.8 nM, respectively. Taken together, these results clearly indicate that 5-[123I]iodo-A-84543 is not suitable for the study of nAChRs in vivo using SPECT.
Assuntos
Encéfalo/metabolismo , Hidrocarbonetos Iodados/química , Piridinas/química , Pirrolidinas/química , Compostos Radiofarmacêuticos/química , Receptores Nicotínicos/análise , Animais , Encéfalo/diagnóstico por imagem , Feminino , Hidrocarbonetos Iodados/síntese química , Hidrocarbonetos Iodados/farmacocinética , Radioisótopos do Iodo , Masculino , Papio , Piridinas/síntese química , Piridinas/farmacocinética , Pirrolidinas/síntese química , Pirrolidinas/farmacocinética , Ensaio Radioligante/métodos , Compostos Radiofarmacêuticos/farmacocinética , Ratos , Ratos Sprague-Dawley , Receptores Nicotínicos/metabolismo , Distribuição Tecidual , Tomografia Computadorizada de Emissão de Fóton Único/métodosAssuntos
Ataxia/etiologia , Carcinoma de Células Pequenas/diagnóstico por imagem , Metástase Linfática/diagnóstico por imagem , Síndromes Paraneoplásicas/etiologia , Transtornos de Sensação/etiologia , Carcinoma de Células Pequenas/complicações , Carcinoma de Células Pequenas/secundário , Fluordesoxiglucose F18 , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Desconhecidas , Cintilografia , Compostos RadiofarmacêuticosRESUMO
OBJECTIVE: Positron emission tomography (PET) scanning is more sensitive at detecting metastatic disease than conventional radiological techniques. For patients with pulmonary metastatic melanoma, we investigate if PET scanning to detect occult extra pulmonary disease prior to thoracotomy and metastectomy is associated with improved survival compared to patients staged by conventional radiology. METHODS: Between November 1984 and December 1999, 121 patients (90 males, 31 females) have undergone a thoracotomy and pulmonary metastectomy for metastatic melanoma. The age range was 19-84 years (mean 57, median 59). In every case all palpable nodules were removed and the diagnosis confirmed histologically. A total of 68 (56%) patients had a PET scan preoperatively, 53 (44%) underwent conventional or nuclear imaging. Patients with only radiologically isolated pulmonary disease are included. RESULTS: Survival is 100% complete and totals 238 pt/years (mean 2.2 years, median 1.4 years). Survival (+/-SE) at 1, 3, 5 and 7 years for all patients is 68% (+/-4.5) (n=67), 36.6% (+/-5.2) (n=27), 22.1% (+/-4.8) (n=15) and 13.5% (+/-4.2) (n=7), respectively. Survival (+/-SE) was significantly better at 3 and 5 years in patients who underwent a PET scan preoperatively (Log rank P=0.002). There was no significant difference in survival by 7 years. CONCLUSIONS: There is a significant survival benefit associated with excluding extra pulmonary disease using a PET scan prior to thoracotomy and metastectomy. We recommend that PET scanning be used in the investigation of patients with pulmonary metastatic melanoma prior to metastectomy.
Assuntos
Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/secundário , Melanoma/mortalidade , Melanoma/secundário , Tomografia Computadorizada de Emissão , Humanos , Pulmão/irrigação sanguínea , Pulmão/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Melanoma/diagnóstico por imagem , Cuidados Pré-Operatórios , Estudos Retrospectivos , Estatística como Assunto , Análise de Sobrevida , Fatores de Tempo , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: The objective of this report is to correlate the clinical outcome of neurosurgery for obsessive-compulsive disorder (OCD) with regional cerebral glucose metabolic changes. CLINICAL PICTURE: The patient was a 37-year-old female patient with severe and intractable OCD. TREATMENT: The patient was treated with bilateral stereotactic lesions in the frontal white matter superior to the orbito-medial cortex. OUTCOME: She had a remarkable improvement in her obsessive-compulsive symptoms, which was sustained up to 3 years of follow up. A positron emission tomography (PET) scan performed 18 days after surgery demonstrated an obvious reduction of metabolism in the caudate head, anterior cingulate and orbital, medial and lateral prefrontal cortices and the thalamus. At 1 year postsurgery, metabolic rate was still reduced in the anterior cingulate gyrus, caudate and thalamus compared with preoperative baseline. The patient demonstrated no long-term cognitive effects of the surgery. CONCLUSIONS: This case supports some of the cortical-subcortical circuit dysfunction models of OCD and argues for the further evaluation of neurosurgery for the treatment of a severe and intractable disorder.
Assuntos
Encéfalo/cirurgia , Transtorno Obsessivo-Compulsivo/cirurgia , Psicocirurgia/métodos , Tomografia Computadorizada de Emissão , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Feminino , Fluordesoxiglucose F18 , Humanos , Testes Neuropsicológicos , Transtorno Obsessivo-Compulsivo/diagnóstico por imagem , Transtorno Obsessivo-Compulsivo/metabolismo , Compostos Radiofarmacêuticos , Radiocirurgia/métodos , Indução de Remissão , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Six cases with a clinical corticobasal syndrome (progressive asymmetric apraxia and parkinsonism unresponsive to levodopa) and tau pathology were selected from 97 brain donors with parkinsonism. Postmortem volumetric measures of regional brain atrophy (compared with age/sex-matched controls) were correlated with clinical features and the degree of underlying cortical and subcortical histopathology. At death, no significant asymmetry of pathology was detected. All cases had prominent bilateral atrophy of the precentral gyrus (reduced by 22-54%) with other cortical regions variably affected. Subcortical atrophy was less severe and variable. Two cases demonstrated widespread atrophy of basal ganglia structures (44-60% atrophy of the internal globus pallidus) and substantial subcortical pathology consistent with a diagnosis of progressive supranuclear palsy (PSP). The remaining four cases had typical pathology of corticobasal degeneration. In all cases, neuronal loss and gliosis corresponded with subcortical atrophy, while the density of cortical swollen neurons correlated with cortical volume loss. Atrophy of the internal globus pallidus was associated with postural instability, while widespread basal ganglia histopathology was found in cases with gaze palsy. This study confirms the involvement of the precentral gyrus in the corticobasal syndrome and highlights the variable underlying pathology in these patients.
Assuntos
Apraxia Ideomotora/patologia , Gânglios da Base/patologia , Córtex Cerebral/patologia , Transtornos Parkinsonianos/patologia , Proteínas tau/análise , Idoso , Atrofia , Encéfalo/patologia , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neurônios/patologia , Paralisia Supranuclear Progressiva/patologiaRESUMO
The effects of mesial temporal (MT) and cerebellar hypometabolism were studied using measures of verbal, visual and motor skill learning. Twelve patients with refractory temporal lobe epilepsy who showed asymmetrical mesial temporal lobe hypometabolism on [18F] fluoro-2-deoxy-glucose positron emission tomography (FDG-PET) were given tests involving 4 consecutive learning trials and a 30-min delayed recall trial. Delayed recognition was also assessed for the words and designs, and skill transfer was evaluated for mirror drawing. Compared to 9 normal control participants, patients with more marked MT hypometabolism on the left had impaired delayed recall of words and patients with more marked MT hypometabolism on the right showed impaired learning of novel designs, but normal retention over delay. Patients were not impaired in their mirror-drawing performance. The findings for MT hypometabolism correspond well to those obtained in other studies where patients have been classified on the basis of side of hippocampal atrophy or temporal lobe excision.
Assuntos
Química Encefálica/fisiologia , Cerebelo/metabolismo , Aprendizagem/fisiologia , Memória/fisiologia , Lobo Temporal/metabolismo , Adulto , Cerebelo/diagnóstico por imagem , Epilepsia do Lobo Temporal/metabolismo , Epilepsia do Lobo Temporal/psicologia , Feminino , Corantes Fluorescentes , Fluordesoxiglucose F18 , Humanos , Masculino , Pessoa de Meia-Idade , Destreza Motora/fisiologia , Cintilografia , Lobo Temporal/diagnóstico por imagemRESUMO
Dynamic imaging with positron emission tomography (PET) is widely used for the in vivo measurement of regional cerebral metabolic rate for glucose (rCMRGlc) with [18F]fluorodeoxy-D-glucose (FDG) and is used for the clinical evaluation of neurological disease. However, in addition to the acquisition of dynamic images, continuous arterial blood sampling is the conventional method to obtain the tracer time-activity curve in blood (or plasma) for the numeric estimation of rCMRGlc in mg glucose/100-g tissue/min. The insertion of arterial lines and the subsequent collection and processing of multiple blood samples are impractical for clinical PET studies because it is invasive, has the remote, but real potential for producing limb ischemia, and it exposes personnel to additional radiation and risks associated with handling blood. In this paper, based on our previously proposed method for extracting kinetic parameters from dynamic PET images, we developed a modified version (post-estimation method) to improve the numerical identifiability of the parameter estimates when we deal with data obtained from clinical studies. We applied both methods to dynamic neurologic FDG PET studies in three adults. We found that the input function and parameter estimates obtained with our noninvasive methods agreed well with those estimated from the gold standard method of arterial blood sampling and that rCMRGlc estimates were highly correlated (r = 0.973). More importantly, no significant difference was found between rCMRGlc estimated by our methods and the gold standard method (P > 0.16). We suggest that our proposed noninvasive methods may offer an advance over existing methods.
Assuntos
Monitorização Fisiológica , Tomografia Computadorizada de Emissão , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Simulação por Computador , Glucose/metabolismo , HumanosRESUMO
To quantify changes in neuronal nAChR binding in vivo, quantitative dynamic SPECT studies were performed with 5-[(123)I]-iodo-A-85380 in baboons pre and post chronic treatment with (-)-nicotine or saline control. Infusion of (-)-nicotine at a dose of 2.0 mg/kg/24h for 14 days resulted in plasma (-)-nicotine levels of 27.3 ng/mL. This is equivalent to that found in an average human smoker (20 cigarettes a day). In the baboon brain the regional distribution of 5-[(123)I]-iodo-A-85380 was consistent with the known densities of nAChRs (thalamus > frontal cortex > cerebellum). Changes in nAChR binding were estimated from the volume of distribution (V(d) ) and binding potential (BP) derived from 3-compartment model fits. In the (-)-nicotine treated animal V(d) was significantly increased in the thalamus (52%) and cerebellum (50%) seven days post cessation of (-)-nicotine treatment, suggesting upregulation of nAChRs. The observed 33% increase in the frontal cortex failed to reach significance. A significant increase in BP was seen in the thalamus. In the saline control animal no changes were observed in V(d) or BP under any experimental conditions. In this preliminary study, we have demonstrated for the first time in vivo upregulation of neuronal nAChR binding following chronic (-)-nicotine treatment.
Assuntos
Azetidinas/farmacocinética , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Radioisótopos do Iodo/farmacocinética , Nicotina/farmacologia , Piridinas/farmacocinética , Receptores Nicotínicos/metabolismo , Regulação para Cima , Animais , Cerebelo/metabolismo , Lobo Frontal/metabolismo , Cinética , Masculino , Papio , Ensaio Radioligante , Compostos Radiofarmacêuticos/farmacocinética , Receptores Nicotínicos/análise , Receptores Nicotínicos/efeitos dos fármacos , Tálamo/metabolismo , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
We investigated the influence of tomograph sensitivity on reliability of parameter estimation in positron emission tomography studies of the rat brain. The kinetics of two tracers in rat striatum and cerebellum were simulated. A typical injected dose of 10 MBq and a reduced dose of 1 MBq were assumed. Kinetic parameters were estimated using a region of interest (ROI) analysis and two pixel-by-pixel analyses. Striatal binding potential was estimated as a function of effective tomograph sensitivity (S(eff)) using a simplified reference tissue model. A S(eff) value of > or =1% was required to ensure reliable parameter estimation for ROI analysis and a S(eff) of 3-6% was required for pixel-by-pixel analysis. We conclude that effective tomograph sensitivity of 3% may be an appropriate design goal for rat brain imaging.
Assuntos
Encéfalo/diagnóstico por imagem , Cocaína/análogos & derivados , Simulação por Computador , Glicoproteínas de Membrana , Proteínas de Membrana Transportadoras , Modelos Neurológicos , Proteínas do Tecido Nervoso , Tomografia Computadorizada de Emissão/métodos , Animais , Encéfalo/metabolismo , Proteínas de Transporte/metabolismo , Cerebelo/diagnóstico por imagem , Cerebelo/metabolismo , Cocaína/farmacocinética , Corpo Estriado/diagnóstico por imagem , Corpo Estriado/metabolismo , Antagonistas de Dopamina/farmacocinética , Antagonistas dos Receptores de Dopamina D2 , Proteínas da Membrana Plasmática de Transporte de Dopamina , Relação Dose-Resposta a Droga , Processamento de Imagem Assistida por Computador , Ligantes , Imagens de Fantasmas , Racloprida/farmacocinética , Radioisótopos/farmacocinética , Ratos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Tomografia Computadorizada de Emissão/normasAssuntos
Neoplasias/diagnóstico por imagem , Tomografia Computadorizada de Emissão , Austrália , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Análise Custo-Benefício , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Genetic mutations in the tau gene on chromosome 17 are known to cause frontotemporal dementias. We have identified a novel silent mutation (S305S) in the tau gene in a subject without significant atrophy or cellular degeneration of the frontal and temporal cortices. Rather the cellular pathology was characteristic of progressive supranuclear palsy, with neurofibrillary tangles concentrating within the subcortical regions of the basal ganglia. Two affected family members presented with symptoms of dementia and later developed neurological deficits including abnormality of vertical gaze and extrapyramidal signs. The third presented with dystonia of the left arm and dysarthria, and later developed a supranuclear gaze palsy and falls. The mutation is located in exon 10 of the tau gene and forms part of a stem-loop structure at the 5' splice donor site. Although the mutation does not give rise to an amino acid change in the tau protein, functional exon-trapping experiments show that it results in a significant 4.8-fold increase in the splicing of exon 10, resulting in the presence of tau containing four microtubule-binding repeats. This study provides direct molecular evidence for a functional mutation that causes progressive supranuclear palsy pathology and demonstrates that mutations in the tau gene are pleiotropic.