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1.
Eur Arch Psychiatry Clin Neurosci ; 262(3): 183-91, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22081145

RESUMO

The aim of this dual-isotope SPECT imaging study was to evaluate striatal dopamine transporter (DAT) and D2 receptor availability in first-episode never-treated and haloperidol-treated schizophrenic patients and whether the availability is associated with psychopathology. Twenty-four inpatients with a first acute schizophrenic episode were enrolled in the study; 12 of these patients were treated with haloperidol for 2 weeks before dual-isotope SPECT was performed, whereas the other 12 patients underwent the SPECT evaluation directly after enrollment. Twelve healthy control persons were also recruited and evaluated with the dual-isotope SPECT protocol. Psychopathology was assessed by the Positive and Negative Syndrome Scale and other scales. D2-radioligand binding did not differ between drug-naïve patients and the control group but was significantly lower in the haloperidol-treated group. DAT availability was also significantly lower in the haloperidol patients than in the other two groups and differed significantly between drug-naïve, positive-syndrome-type patients and healthy controls. The data obtained with the new dual-isotope SPECT technique reveal a direct effect of haloperidol at the D2 and DAT receptor level.


Assuntos
Corpo Estriado/diagnóstico por imagem , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Esquizofrenia/patologia , Tomografia Computadorizada de Emissão de Fóton Único , Adolescente , Adulto , Análise de Variância , Benzamidas/farmacocinética , Corpo Estriado/efeitos dos fármacos , Antagonistas de Dopamina/farmacologia , Antagonistas de Dopamina/uso terapêutico , Feminino , Haloperidol/farmacologia , Haloperidol/uso terapêutico , Humanos , Masculino , Compostos de Organotecnécio/farmacocinética , Ligação Proteica/efeitos dos fármacos , Escalas de Graduação Psiquiátrica , Pirrolidinas/farmacocinética , Compostos Radiofarmacêuticos/farmacocinética , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/tratamento farmacológico , Tropanos/farmacocinética , Adulto Jovem
2.
Ann Surg Oncol ; 17(9): 2357-62, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20217256

RESUMO

BACKGROUND: There is some evidence that sentinel lymph node (SLN) biopsy guided by dye injection and/or radioisotopes can improve staging of inguinal lymph nodes (LNs) in anal cancer. This study was performed to investigate the feasibility of fluorescence detection of SLN and lymphatic mapping in anal cancer. METHODS: Twelve patients with anal cancer without evidence for inguinal LN involvement were included in the study. Intraoperatively, all patients received a peritumorous injection of 25 mg indocyanine green (ICG) for fluorescence imaging of the SLN with a near-infrared camera. For comparison, conventional SLN detection by technetium-(99)m-sulfur radiocolloid injection in combination with blue dye was also performed in all patients. The results of both techniques and the effect on the therapeutic regimen were analyzed. RESULTS: Overall, ICG fluorescence imaging identified at least one SLN in 10 of 12 patients (detection rate, 83%). With the combination of radionuclide and blue dye, SLN were detected in 9 of 12 patients (detection rate, 75%). Metastatic involvement of the SLN was found in 2 of 10 patients versus 2 of 9 patients. Patients with metastatic involvement of the SLN received extended radiation field with inguinal boost. CONCLUSIONS: ICG fluorescence imaging allows intraoperative lymphatic mapping and transcutaneous SLN detection for selective biopsy of inguinal SLN in anal cancer. This technique should be further evaluated in comparative studies with larger patient numbers.


Assuntos
Neoplasias do Ânus/patologia , Verde de Indocianina , Linfonodos/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Ânus/diagnóstico por imagem , Neoplasias do Ânus/cirurgia , Corantes , Estudos de Viabilidade , Feminino , Humanos , Linfonodos/diagnóstico por imagem , Linfonodos/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Prognóstico , Cintilografia , Compostos Radiofarmacêuticos , Biópsia de Linfonodo Sentinela , Coloide de Enxofre Marcado com Tecnécio Tc 99m , Adulto Jovem
3.
Br J Surg ; 96(11): 1289-94, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19847873

RESUMO

BACKGROUND: Sentinel lymph node (SLN) biopsy with radioisotope and blue dye has been used successfully for axillary staging in breast cancer. This study evaluated the feasibility of fluorescence detection of SLNs with indocyanine green (ICG) for lymphatic mapping and SLN biopsy. METHODS: Thirty women with breast cancer had a periareolar injection of ICG for fluorescence detection of SLN using a near-infrared camera. Twenty also received (99m)Tc-labelled sulphur radiocolloid for SLN scintigraphy. All patients underwent axillary lymph node dissection. Detection rate and sensitivity of both methods were the study endpoints. RESULTS: Visualization of lymphatic vessels by fluorescence detection depended on the dose of ICG. ICG imaging identified SLNs in 29 of 30 women (detection rate 97 per cent). Nineteen of 21 patients had metastatic SLN involvement (sensitivity 90 per cent) with false-negative results in two. Among the 20 patients who had both methods, ICG fluorescence and radiocolloid identified SLNs in 20 and 17 patients respectively. Metastatic lymph nodes were diagnosed in 12 and ten of 13 patients (sensitivity 92 and 77 per cent). False-negative rates were 8 and 23 per cent respectively. CONCLUSION: ICG fluorescence allowed transcutaneous imaging of lymphatic vessels and SLN detection, thus combining the advantages of radioisotope and blue dye methods.


Assuntos
Neoplasias da Mama/patologia , Mama/patologia , Corantes , Verde de Indocianina , Biópsia de Linfonodo Sentinela/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/cirurgia , Carcinoma Lobular/patologia , Carcinoma Lobular/cirurgia , Estudos de Viabilidade , Feminino , Humanos , Excisão de Linfonodo/métodos , Metástase Linfática , Mastectomia/métodos , Pessoa de Meia-Idade
4.
Schizophr Res ; 101(1-3): 133-41, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18083348

RESUMO

OBJECTIVE: The aim of this investigation was to evaluate the usefulness of a dual-isotope SPECT technique to assess simultaneously striatal dopamine binding structures - presynaptic dopamine transporter (DAT) and postsynaptic dopamine D(2) receptor - in first-episode, drug-naive schizophrenic patients compared to healthy control persons. Additionally, relations between radioligand binding to DAT and D(2) and positive symptoms were assessed. METHODS: Twenty acutely ill inpatients suffering from a first acute schizophrenic episode and 12 healthy control persons participated in the study. Patients were naïve with respect to neuroleptic or antidepressant medication. A dual-isotope SPECT protocol was performed using combined application of [99mTc]TRODAT-1 and [123I]IBZM. On the day of SPECT, psychopathology was assessed in the patient group by PANSS rating. RESULTS: In the patient but not in the healthy control group there was a significant correlation between DAT and D(2) receptor availability. Patients with predominant positive symptoms (n=12) had a significantly higher DAT availability compared to the healthy control group. An inverse correlation between DAT and D(2) availability and the extent of "delusions", "conceptual disorganization", and "hallucinatory behaviour" could be demonstrated. DISCUSSION: The data obtained with this dual-isotope SPECT technique show a change in interaction between striatal DAT and D(2) receptor in first-episode, never-treated schizophrenic patients. Additionally, an association between dopamine transmission and the core symptoms of the acute psychotic syndrome was found.


Assuntos
Corpo Estriado/diagnóstico por imagem , Dopamina/metabolismo , Esquizofrenia/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único , Adulto , Análise de Variância , Benzamidas , Corpo Estriado/metabolismo , Feminino , Humanos , Masculino , Compostos de Organotecnécio , Escalas de Graduação Psiquiátrica , Pirrolidinas , Esquizofrenia/metabolismo , Esquizofrenia/patologia , Tropanos
5.
J Clin Oncol ; 15(7): 2683-90, 1997 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9215841

RESUMO

PURPOSE: The aim of this phase II study was to assess the clinical utility and safety of AFP-Scan (Immunomedics, Inc, Morris Plains, NJ), a technetium-99m (99mTc)-labeled anti-alpha-fetoprotein (AFP) Fab' imaging kit, in the evaluation of hepatocellular carcinoma (HCC), in comparison to computed tomography (CT). PATIENTS AND METHODS: Twenty-five consecutive patients with a history of HCC were examined by planar and single-photon emission computed tomography (SPECT) imaging at 6 and 24 hours after intravenous (I.V.) injection of 1 mg AFP-Scan labeled with 925 MBq 99mTc. RESULTS: In 20 patients, there was a specific binding of the Fab' antibody to the tumor, whereas in four patients who presented with elevated serum AFP levels, no specific targeting was found and no malignant lesions were evident by CT or biopsy. One patient was diagnosed as false-negative by AFP-Scan. In five of six patients with normal serum AFP levels, focal uptake was demonstrated. In one case, metastatic disease in the lower abdomen was found. In all patients, diagnostically relevant information was provided by the 24-hour antibody images, especially with SPECT. Comparing AFP-Scan versus CT, the former showed a higher sensitivity (95% v 63%) and specificity (67% v 17%), with an overall accuracy of 88% versus 52% for AFP-Scan versus CT, even in patients with normal serum AFP titers. No adverse reactions or human antimouse antibody (HAMA) elevations were found in any of the patients. CONCLUSIONS: AFP-Scan appears to be a promising new antibody imaging kit for the disclosure of sites of HCC and should aid in the management of these patients by revealing primary, recurrent, and metastatic disease with a single imaging modality.


Assuntos
Anticorpos Antineoplásicos/sangue , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Kit de Reagentes para Diagnóstico , alfa-Fetoproteínas/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/imunologia , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/imunologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Compostos Radiofarmacêuticos , Pertecnetato Tc 99m de Sódio , Tomografia Computadorizada de Emissão de Fóton Único , Tomografia Computadorizada por Raios X , alfa-Fetoproteínas/metabolismo
6.
Diabetes ; 45(6): 801-5, 1996 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-8635656

RESUMO

123I-labeled metaiodobenzylguanidine (123I-MIBG) scintigraphy is a novel technique for the assessment of cardiac sympathetic dysinnervation. To evaluate defects of the cardiac autonomic nervous system at the onset of IDDM, this technique together with conventional electrocardiogram (ECG)-based cardiac reflex tests and measurement of the QT interval was applied to 22 newly diagnosed metabolically stabilized IDDM patients without myocardial perfusion abnormalities (99mTc-labeled methoxyisobutylisonitrile scintigraphy) and 9 matched control subjects. Seventeen diabetic patients (77%), but none of the control subjects, were observed to have a reduced global myocardial uptake of 123I-MIBG. In contrast, only two diabetic patients (9%) demonstrated an ECG-based cardiac autonomic neuropathy (two or more of five age-related cardiac reflex tests abnormal) (P < 0.001). In newly diagnosed IDDM patients, the uptake of 123I-MIBG was reduced more in the posterior myocardial region compared with the lateral and apical region (P < 0.01, P = 0.03). The septal myocardial region exhibited a smaller uptake than the lateral myocardial region (P = 0.02). The maximum/minimum 30:15 ratio correlated with the global, anterior, lateral, and septal myocardial uptake of 123I-MIBG (P < 0.05, P < 0.05, P < 0.01, P < 0.05). A correlation between global and regional myocardial 123I-MIBG uptake and HbA1c or QT interval was not observed. Newly diagnosed metabolically stabilized IDDM patients without myocardial perfusion defects show evidence of cardiac sympathetic dysinnervation, as indicated by a reduction of 123I-MIBG uptake, at a significant higher proportion than ECG-based cardiac autonomic neuropathy. Furthermore, they present with regional differences of myocardial 123I-MIBG uptake.


Assuntos
Diabetes Mellitus Tipo 1/metabolismo , Coração/diagnóstico por imagem , Iodobenzenos/farmacocinética , Miocárdio/metabolismo , 3-Iodobenzilguanidina , Adulto , Glicemia/metabolismo , Meios de Contraste , Diabetes Mellitus Tipo 1/fisiopatologia , Feminino , Coração/fisiopatologia , Frequência Cardíaca , Humanos , Radioisótopos do Iodo/farmacocinética , Masculino , Cintilografia , Respiração , Sístole , Tecnécio Tc 99m Sestamibi/farmacocinética , Manobra de Valsalva
7.
J Psychopharmacol ; 19(5): 488-93, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16166186

RESUMO

Following the current hypothesis that acute schizophrenic psychotic illness is associated with a striatal 'hyperdopaminergic state', presynaptic integrity and dopamine transporter (DAT) density in first-episode, neuroleptic-naive schizophrenic patients was measured by single-photon-emission-tomography (SPECT) and compared with that in healthy control subjects. A new SPECT-ligand for assessment of the striatal DAT, the Technetium-99m-labelled tropane TRODAT-1 ([99mTc]TRODAT-1), was used. Ten inpatients suffering from a first acute schizophrenic episode and 10 age- and sex-matched healthy control subjects underwent SPECT with [99mTc]TRODAT-1. On the day of SPECT, psychopathological ratings were performed with the Brief Psychiatric Rating Scale (BPRS), the Positive and Negative Syndrome Scale (PANSS) and Schedule for Assessment of Negative Symptoms (SANS). Patients had not previously received any neuroleptic or antidepressant medication. Mean specific TRODAT-1 binding in the striatum did not differ significantly between the patient and the age- and sex-matched control group (1.25 vs. 1.28). Variance was significantly higher in the patient group. The data obtained with the new ligand in first-episode, drug-naive schizophrenic patients are in line with the PET results from the group of Laakso et al. in a comparable patient sample. [99mTc]TRODAT-1 seems to be a valuable new SPECT-ligand in the evaluation of the presynaptic site of the striatal dopaminergic synapse in schizophrenia.


Assuntos
Corpo Estriado/metabolismo , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Compostos de Organotecnécio , Esquizofrenia Paranoide/diagnóstico , Tropanos , Doença Aguda , Adulto , Análise de Variância , Ligação Competitiva , Escalas de Graduação Psiquiátrica Breve , Feminino , Humanos , Pacientes Internados , Masculino , Compostos de Organotecnécio/metabolismo , Ligação Proteica , Ensaio Radioligante , Esquizofrenia Paranoide/metabolismo , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Tropanos/metabolismo
8.
J Nucl Med ; 41(11): 1823-9, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11079489

RESUMO

UNLABELLED: A wide range of techniques for registration of medical images has been devised in recent years. The aim of this study is to quantify the overall spatial registration error of 3 different methods for image registration: interactive matching, surface matching, and uniformity index matching as described by Woods. METHODS: MRI and ethylcysteinate dimer-SPECT images of the brain were registered for 15 patients. The matching error was assessed by determining intra- and interobserver variability of registrations. Quantification of the registration error was based on the mean spatial distance of 5000 voxels between 2 image positions. The mean position after repeated registrations in each patient was used as the gold standard. To evaluate the coherence of the 3 different registration methods, intermethod variability was determined. RESULTS: Interactive matching showed an intraobserver/interobserver variability of 1.5+/-0.3 mm/1.6+/-0.3 mm (mean +/- SD). The time demand for this method was 11+/-5 min. Surface matching revealed a variability of 2.6+/-1.1 mm/3.8+/-1.0 mm and a time demand of 26+/-12 min. Reproducibility of Woods' algorithm was 2.2+/-0.8 mm with a time demand of 9+/-3 min. In 4 of the 15 cases, Woods' method failed. The mean deviation between all 3 methods was 2.3+/-0.8 mm. CONCLUSION: With a suitable user interface, interactive matching had the lowest registration error. The influence of subjectivity was shown to be negligible. Therefore, interactive matching is our preferred technique for image fusion of the brain.


Assuntos
Encéfalo/anatomia & histologia , Encéfalo/diagnóstico por imagem , Imageamento Tridimensional , Imageamento por Ressonância Magnética , Tomografia Computadorizada de Emissão de Fóton Único , Adulto , Idoso , Humanos , Pessoa de Meia-Idade , Variações Dependentes do Observador , Estudos Retrospectivos
9.
J Nucl Med ; 39(7): 1138-42, 1998 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9669383

RESUMO

UNLABELLED: The recently introduced neuroleptic, risperidone, was expected to block fewer dopamine D2 receptors than typical neuroleptics (e.g., haloperidol), but at comparable potency. The aim of this study was to evaluate the degree of dopamine D2 receptor occupancy in relation to the neuroleptic dosage and to correlate the findings with the presence of extrapyramidal symptoms (EPS). Additionally, the data were compared to previous iodobenzamide (IBZM) SPECT findings in patients treated with other neuroleptics, haloperidol and clozapine. METHODS: In 20 patients with schizophrenia [Diagnostic and Statistical Manual of Mental Disorders (Third Edition-Revised)] treated with mean daily doses of risperidone ranging from 0.029 to 0.128 mg/kg body weight, SPECT was performed 2 hr after intravenous injection of 185 MBq 123I-IBZM, a selective dopamine D2 receptor ligand. Striatal IBZM binding was assessed by calculating a striatal/frontal cortex ratio, expressed as a percentage of the control value. RESULTS: Selective dopamine D2 receptor binding of the ligand was reduced in all treated patients, with binding values ranging from 7% to 68%. The degree of occupancy displayed an exponential dose-response relationship (r = -0.86; p < 0.0001). The slope of the curve was between those of haloperidol and clozapine but was closer and more similar in shape to the curve of haloperidol. Extrapyramidal symptoms were observed in 8 of 20 patients with binding values between 7% and 47%. However, there was no clear relationship between the degree of receptor occupancy and the presence of EPS. CONCLUSION: The findings suggest an exponential dose-response relationship between the daily dosage of risperidone and the dopamine D2 receptor occupancy. The blockade of specific striatal IBZM binding found under therapy with risperidone is between those of haloperidol and clozapine. The dose-response curve for risperidone, however, shows greater similarity to that of haloperidol.


Assuntos
Antipsicóticos/uso terapêutico , Benzamidas , Encéfalo/diagnóstico por imagem , Radioisótopos do Iodo , Pirrolidinas , Receptores de Dopamina D2/metabolismo , Risperidona/uso terapêutico , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/tratamento farmacológico , Tomografia Computadorizada de Emissão de Fóton Único , Adulto , Antipsicóticos/administração & dosagem , Doenças dos Gânglios da Base/induzido quimicamente , Clozapina/administração & dosagem , Clozapina/uso terapêutico , Meios de Contraste , Relação Dose-Resposta a Droga , Feminino , Haloperidol/administração & dosagem , Haloperidol/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Receptores de Dopamina D2/efeitos dos fármacos , Risperidona/administração & dosagem
10.
J Nucl Med ; 39(12): 2069-76, 1998 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9867143

RESUMO

UNLABELLED: Technetium-99m TRODAT-1 is an analog of cocaine that selectively binds the presynaptic dopamine transporters. The primary purpose of this study was to measure its whole-body biokinetics and radiation dosimetry in healthy human volunteers. The study was conducted within a regulatory framework that required its pharmacological safety to be assessed simultaneously. METHODS: The sample included 4 men and 6 women ranging in age from 22-54 yr. An average of 20 whole-body scans were acquired sequentially on a dual-head camera for up to 46 hr after the intravenous administration of 370+/-16 MBq (10.0+/-0.42 mCi) 99mTc TRODAT. The renal excretion fractions were measured from 12-24 discrete urine specimens. The fraction of the administered dose in 17 regions of interest and each urine specimen was quantified from the attenuation and background corrected geometric mean counts in conjugate views. Multiexponential functions were iteratively fit to each time-activity curve using a nonlinear, least squares regression algorithm. These curves were numerically integrated to yield source organ residence times. Gender-specific radiation doses were then estimated with the Medical Internal Radiation Dose technique for each subject individually before any results were averaged. RESULTS: There were no pharmacological effects of the radiotracer on any of the subjects. The early planar images showed differentially increased activity in the nose, pudendum and stomach. SPECT images demonstrated that the radiopharmaceutical localized in the basal ganglia in a distribution that was consistent with selective transporter binding. Image analysis showed that the kidneys excreted between 20% and 32% of the injected dose during the first 22-28 hr postadministration, after which no more activity could be recovered in the urine. The dose limiting organ in both men and women was the liver, which received an average of 0.046 mGy/MBq (0.17 rads/mCi, range 0.14-0.22 rad/mCi). In the worst case, which was clearly an over-estimation, it would have taken 22.7 mCi to deliver 5 rad to the liver. CONCLUSION: TRODAT may be a safe and effective radiotracer for imaging dopamine transporters in the brain and the body.


Assuntos
Encéfalo/metabolismo , Proteínas de Transporte/metabolismo , Glicoproteínas de Membrana , Proteínas de Membrana Transportadoras , Proteínas do Tecido Nervoso , Compostos de Organotecnécio/farmacocinética , Compostos Radiofarmacêuticos/farmacocinética , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Tropanos/farmacocinética , Adulto , Encéfalo/diagnóstico por imagem , Proteínas de Transporte/análise , Proteínas da Membrana Plasmática de Transporte de Dopamina , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Injeções Intravenosas , Cinética , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Distribuição Tecidual
11.
J Nucl Med ; 40(4): 625-30, 1999 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10210221

RESUMO

UNLABELLED: 99mTc-labeled anti-stage specific embryonic antigen-1 (anti-SSEA-1) is an injectable IgM antibody derived from mice. It binds to CD15 antigens on some granulocytic subpopulations of human white blood cells in vivo after systemic administration. The purpose of this study was to measure biodistribution of 99mTc-labeled anti-SSEA-1 and perform radiation dosimetry in 10 healthy human volunteers. METHODS: Transmission scans and whole-body images were acquired sequentially on a dual-head camera for 32 h after the intravenous administration of about 370 MBq (10.0 mCi) of the radiopharmaceutical. Renal excretion fractions were measured from 10 to 14 discrete urine specimens voided over 27.9 +/- 2.0 h. Multiexponential functions were fit iteratively to the time-activity curves for 17 regions of interest using a nonlinear least squares regression algorithm. The curves were integrated numerically to yield source organ residence times. Gender-specific radiation doses were then estimated individually for each subject, using the MIRD technique, before any results were averaged. RESULTS: Quantification showed that the kidneys excreted 39.5% +/- 6.5% of the administered dose during the first 24 h after administration. Image analysis showed that 10%-14% of the radioactivity went to the spleen, while more than 40% went to the liver. Residence times were longest in the liver (3.37 h), followed by the bone marrow (1.09 h), kidneys (0.84 h) and the spleen (0.65 h). The dose-limiting organ in both men and women was the spleen, which received an average of 0.062 mGy/MBq (0.23 rad/mCi, range 0.08-0.30 rad/mCi), followed by the kidneys (0.051 mGy/MBq), liver (0.048 mGy/MBq) and urinary bladder (0.032 mGy/MBq). The effective dose equivalent was 0.018 mSv/MBq (0.068 rem/mCi). CONCLUSION: The findings suggest that the radiation dosimetry profile for this new infection imaging agent is highly favorable.


Assuntos
Antígenos CD15/imunologia , Radioimunodetecção , Adulto , Algoritmos , Animais , Anticorpos Monoclonais/farmacocinética , Feminino , Granulócitos , Humanos , Imunoglobulina M , Masculino , Camundongos , Doses de Radiação , Compostos Radiofarmacêuticos/farmacocinética , Análise de Regressão , Pertecnetato Tc 99m de Sódio , Distribuição Tecidual
12.
J Nucl Med ; 40(4): 660-6, 1999 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10210226

RESUMO

UNLABELLED: The central nervous system dopamine transporters (DATs) and dopamine D2/D3 receptors are implicated in a variety of neurological disorders. Both sites are also targets for drug treatment. With the successful development of [99mTc]TRODAT-1, single-isotope imaging studies using this ligand for DAT imaging can be complemented by additional use of 123I-labeled D2/D3 receptor ligand co-injected to assess both pre- and postsynaptic sites of the dopaminergic system simultaneously. METHODS: Twelve SPECT scans of the brain were obtained in two baboons after intravenous administration of 740 MBq (20 mCi) [99mTc]-TRODAT-1 (technetium, [2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3,2,1]oct-2-yl]methyl ](2-mercaptoethyl) amino]ethyl]-amino]ethanethiolato (3-)]- oxo-[1R-(exo-exo)]) and 185 MBq (5 mCi) [123I]iodobenzamide or [123I]iodobenzofuran. SPECT data were acquired by a triple-head gamma camera equipped with ultra-high-resolution fanbeam collimators (scan duration = 210 min). Two sets of SPECT data were obtained using energy windows of 15% centered on 140 keV for 99mTc and 10% asymmetric with a lower bound at 159 keV for 123I. After coregistration with MRI, region-of-interest analysis was performed using predefined templates from coregistered MRI. In blocking studies, baboons were pretreated with N-methyl-2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane (CFT, 14 mg) or raclopride (14 mg) to block DAT or D2/D3 binding site, respectively. RESULTS: Image quality of dual-isotope studies was similar to that obtained from single-isotope studies. When one site was blocked with CFT or raclopride, the binding of the respective ligand to the other site was not affected. CONCLUSION: This is the first example that clearly demonstrates the feasibility of simultaneous imaging of both pre- and postsynaptic sites of the dopaminergic system in baboons with dual-isotope SPECT studies. With or without corrections for cross-contamination of 123I into the 99mTc window, striatum-to-cerebellum ratios (target-to-nontarget) of dual-isotope experiments did not differ significantly from single-isotope experiments. This method may be a valuable and cost-effective tool for gaining comprehensive information about the dopaminergic system in one SPECT imaging session.


Assuntos
Encéfalo/diagnóstico por imagem , Proteínas de Transporte/metabolismo , Dopamina/metabolismo , Glicoproteínas de Membrana , Proteínas de Membrana Transportadoras , Proteínas do Tecido Nervoso , Receptores Dopaminérgicos/metabolismo , Tomografia Computadorizada de Emissão de Fóton Único , Animais , Benzamidas , Benzofuranos , Encéfalo/metabolismo , Cocaína/análogos & derivados , Cocaína/farmacologia , Antagonistas de Dopamina/farmacologia , Proteínas da Membrana Plasmática de Transporte de Dopamina , Inibidores da Captação de Dopamina/farmacologia , Feminino , Radioisótopos do Iodo , Compostos de Organotecnécio , Papio , Pirrolidinas , Racloprida , Compostos Radiofarmacêuticos , Salicilamidas/farmacologia , Tropanos
13.
J Nucl Med ; 40(1): 150-8, 1999 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9935071

RESUMO

UNLABELLED: [99mTc]Technetium[2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo [3.2.1] oct-2-yl]-methyl] (2-mercaptoethyl) amino] ethyl] amino] ethane-thiolato(3-)-N2,N2',S2,S2']oxo-[1R-(exo-exo)] ([99mTc] TRODAT-1) is a useful imaging agent for central nervous system dopamine transporters. The purpose of this study was to characterize the in vivo binding potential and kinetic rate constants of this agent in nonhuman primates. METHODS: A series of four SPECT scans were performed on each of two female baboons with a bolus injection of [99mTc]TRODAT-1 (717+/-78 MBq; 19.38+/-2.12 mCi). Dynamic images of the brain were acquired over 4 h using a triple-head camera equipped with fan-beam collimators. Arterial and venous blood were sampled frequently using a peristaltic pump throughout the duration of the study. Regions of interest were drawn on the corresponding MRI scan to which each functional image was coregistered. Using analytical solutions to the three-compartment model with the Levenberg-Marquardt minimization technique, each study was individually fitted to a kinetic parameter vector (method I). Additionally, within each subject, three corresponding intrasubject studies were fitted simultaneously to a single parameter vector by constraining the binding potential, distribution volume and dissociation rate constant to improve the identifiability of the parameter estimates (method II). RESULTS: The results clearly indicated that [99mTc] TRODAT-1 localized in the striatum with slower washout rate than other brain regions. A maximal target/nontarget ratio of 3.5 between striatum and cerebellum was obtained. SPECT image analysis of the striatum yielded unconstrained k3/k4 values of 3.4+/-1.4, 2.4+/-0.7, 3.0+/-1.5, and 4.0+/-10.3, with respective constrained (fixed k4) values of 2.9 +/- 0.4, 2.4 +/- 0.4, 1.7+/-0.4 and 1.8+/-0.4 in one baboon using method I. With method II, the corresponding simultaneously fitted values were 2.1+/-0.3 using no constraints and 2.2+/-0.2 using a fixed k4. The second baboon had similar results. CONCLUSION: These findings suggest that the binding potential and corresponding kinetic rate constants can be reliably estimated in nonhuman primates with dynamic SPECT imaging of the dopamine transporter using a technetium-based tropane analogue. Furthermore, method II parameter vectors compare favorably to those produced using method I based on SEEs.


Assuntos
Encéfalo/metabolismo , Proteínas de Transporte/metabolismo , Dopamina/metabolismo , Glicoproteínas de Membrana , Proteínas de Membrana Transportadoras , Proteínas do Tecido Nervoso , Compostos de Organotecnécio , Tropanos , Animais , Encéfalo/diagnóstico por imagem , Proteínas da Membrana Plasmática de Transporte de Dopamina , Feminino , Humanos , Compostos de Organotecnécio/farmacocinética , Papio , Tomografia Computadorizada de Emissão de Fóton Único , Tropanos/farmacocinética
14.
J Clin Psychiatry ; 61(8): 585-93, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10982202

RESUMO

BACKGROUND: The rare cases of patients with 48-hour ultrarapid cycling allow close investigation of mood cycles in affective disorders, because rhythmic changes in psychopathologic state and biological parameters happen very precisely. METHOD: A 67-year-old white man who had experienced bipolar 48-hour ultrarapid cycling (DSM-IV 296.80) for several years was studied without any medication and then again studied 4 weeks later during treatment with valproate (1800 mg/day). RESULTS: Objective and self ratings revealed pronounced manic states 1 day and depressed states the following day, which were found to be accompanied by rhythmic fluctuations in behavior and electroencephalographic parameters, blood cortisol and growth hormone levels (both elevated on depressive days), and urinary metanephrine (dopamine metabolite) and norepinephrine levels (both elevated on manic days). Using single photon emission computed tomography, regional blood flow in the left thalamus was lower than in the right thalamus on the manic day, while symmetric perfusion of the thalamus was found on the depressive day. Under valproate treatment, the patient remitted completely, and significant rhythmic changes in most of the biological parameters were no longer detectable. CONCLUSION: The biological findings in this patient with bipolar 48-hour ultrarapid cycling, which correspond to those in other types of affective disorders, suggest that disturbances in the diencephalon-pituitary axis may be especially correlated to pathologic changes of mood.


Assuntos
Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/psicologia , Periodicidade , Ácido Valproico/uso terapêutico , Idoso , Transtorno Bipolar/diagnóstico por imagem , Transtorno Bipolar/fisiopatologia , Transtorno Depressivo/diagnóstico por imagem , Transtorno Depressivo/tratamento farmacológico , Transtorno Depressivo/fisiopatologia , Lateralidade Funcional/fisiologia , Hormônio do Crescimento Humano/sangue , Humanos , Masculino , Fluxo Sanguíneo Regional , Tálamo/irrigação sanguínea , Tálamo/diagnóstico por imagem , Tálamo/fisiopatologia , Tomografia Computadorizada de Emissão de Fóton Único , Resultado do Tratamento
15.
Neurosci Lett ; 285(2): 107-10, 2000 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-10793238

RESUMO

Ten previously untreated adults with attention deficit hyperactivity disorder (ADHD) were investigated before and after 4 weeks of treatment with a dose of 3x5 mg methylphenidate/d by single photon emission computed tomography (SPECT) with [Tc-99m]TRODAT-1, the first Tc-99m labelled SPECT ligand specifically binding to the dopamine transporter (DAT). For semiquantitative evaluation of the DAT, specific binding ([STR-BKG]/BKG) was calculated in the striatum (STR) with the cerebellum used as background (BKG). The patients with ADHD presented with increased specific binding of Tc-99m-TRODAT-1 to the DAT as compared with age and sex matched controls ([STR-BKG]/BKG 1.43+/-0.18 vs. 1.22+/-0.05, P<0.001). After treatment with methylphenidate specific binding decreased in all patients ([STR-BKG]/BKG 1.02+/-0.23, P<0.001). Thus, for the first time it could be demonstrated using SPECT that methylphenidate lowers increased striatal DAT availability in adults suffering from ADHD.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/metabolismo , Proteínas de Transporte/metabolismo , Corpo Estriado/química , Glicoproteínas de Membrana , Proteínas de Membrana Transportadoras , Metilfenidato/farmacologia , Proteínas do Tecido Nervoso , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico por imagem , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/patologia , Proteínas da Membrana Plasmática de Transporte de Dopamina , Feminino , Humanos , Masculino , Metilfenidato/administração & dosagem , Metilfenidato/uso terapêutico , Pessoa de Meia-Idade , Compostos de Organotecnécio , Radiografia , Compostos Radiofarmacêuticos , Tomografia Computadorizada de Emissão de Fóton Único , Tropanos
16.
AJNR Am J Neuroradiol ; 14(6): 1329-31, 1993.
Artigo em Inglês | MEDLINE | ID: mdl-8279327

RESUMO

The clinical and MR findings in an unusual case of gummatous neurosyphilis are reported. A 44-year-old woman suffering from diplopia and right-sided headaches was admitted. Physical examination and routine laboratory parameters were normal except for a third-nerve palsy. MR images revealed a contrast-enhancing lesion of the upper brain stem and third cranial nerve. Differential diagnosis included neuroma of the third cranial nerve, as well as neurosarcoidosis and other inflammatory processes. Serologic tests and lumbar puncture revealed the presence of active syphilis. After intravenous treatment with penicillin G, follow-up MR examinations showed diminishing size of the lesion with its complete resolution within 3 months.


Assuntos
Imageamento por Ressonância Magnética , Neurossífilis/complicações , Doenças do Nervo Oculomotor/etiologia , Adulto , Encéfalo/patologia , Diagnóstico Diferencial , Feminino , Humanos , Neurossífilis/diagnóstico , Neurossífilis/patologia , Doenças do Nervo Oculomotor/diagnóstico
17.
AJNR Am J Neuroradiol ; 11(1): 187-94, 1990.
Artigo em Inglês | MEDLINE | ID: mdl-2105604

RESUMO

The purpose of this study was to describe our experience with Gd-DTPA-enhanced MR imaging in the evaluation of the most common nasopharyngeal tumors. Forty-two patients with tumors of the nasopharynx and adjacent spaces had MR imaging before and after IV injection of Gd-DTPA. Images were obtained with a 1.0-T superconducting magnet imaging system in transverse, coronal, and sagittal planes with T1- and T2-weighted sequences. MR images were compared with CT scans and tumor histology. The studies were categorized by using a grading system with grades ranging from unsatisfactory (grade 0) to optimal (grade 3). Contrast-enhanced MR enables better identification of small anatomic details such as both palatini muscles and the pharyngobasilar fascia. MR after Gd-DTPA was superior to CT in all cases except for tumors of the maxillary sinuses. MR with Gd-DTPA is recommended for tumors that are small and difficult to detect on the initial nonenhanced MR examination or that show subtle infiltrations. Because of the increased cost and longer examination time, MR with Gd-DTPA does not need to be done when large tumors are well delineated.


Assuntos
Carcinoma de Células Escamosas/diagnóstico , Gadolínio , Neoplasias Nasofaríngeas/diagnóstico , Compostos Organometálicos , Ácido Pentético , Carcinoma de Células Escamosas/secundário , Meios de Contraste , Gadolínio DTPA , Humanos , Imageamento por Ressonância Magnética , Neoplasias Nasofaríngeas/secundário
18.
Nucl Med Biol ; 28(4): 383-9, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11395310

RESUMO

[(123)I]AIBZM, (S)-5-[(123)I]-Iodo-N-[(1-ethyl-2-pyrrolidinyl)]methyl-4-amine-2-methoxybenzamide is a derivative with high affinity for the D2 receptor. Labeling was achieved by the Iodogen method. The in vivo affinity for the D2 receptor and the biological characteristics were performed in rats. The brain uptake of [(123)I]AIBZM was significantly lower, however the striatum/cerebellum ratio (2h p.i.) was higher than that of [(123)I]IBZM. Because of the high affinity and its possibly lower unspecific binding compared to [(123)I]IBZM, [(123)I]AIBZM may be a potential imaging agent for the D2 dopamine receptor.


Assuntos
Benzamidas/farmacocinética , Encéfalo/diagnóstico por imagem , Pirrolidinas/farmacocinética , Compostos Radiofarmacêuticos/farmacocinética , Receptores de Dopamina D2/metabolismo , Animais , Autorradiografia , Proteínas Sanguíneas/metabolismo , Química Encefálica , Fenômenos Químicos , Físico-Química , Ligação Proteica , Cintilografia , Ratos , Ratos Sprague-Dawley , Distribuição Tecidual
19.
J Psychopharmacol ; 14(4): 364-70, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11198054

RESUMO

The aim of this study was to compare the degree of striatal dopamine D2 receptor availability in patients treated with recommended (5-20 mg, mean dose 11.9 +/- 6.3 mg daily) and higher doses (25-40 mg, mean 32.1 +/- 5.6 mg daily) of the novel antipsychotic drug olanzapine by means of [123I] IBZM Single photon emission computed tomography (SPECT). The results were compared to those of a group of 10 untreated, healthy, age- and sex-matched controls. The degree of dopamine D2 receptor occupancy in the patient group was correlated with the presence of extrapyramidal symptoms (EPS). A total of 20 patients who met the DSM III R criteria for schizophrenia or schizoaffective disorder received a clinically effective antipsychotic monotherapy with olanzapine. The mean daily dose of olanzapine ranged from 0.05-0.6 mg/kg body weight. The dopamine D2 receptor binding was reduced in all patients treated with olanzapine. Specific IBZM binding expressed as the [STR-BKG]/BKG ratio ranged from 0.13-0.61 (healthy controls 0.95). The D2 receptor availability revealed an exponential dose-response relationship (r = - 0.85, p < 0.001). The frequency of EPS induced by olanzapine was considerably lower. Only one patient, treated with 40 mg olanzapine, suffered from severe EPS symptoms and had to be given biperiden. There were no significant differences in the presence of EPS symptoms between patients with recommended doses and those with higher doses of olanzapine.


Assuntos
Antipsicóticos/farmacocinética , Benzamidas , Pirenzepina/análogos & derivados , Pirenzepina/farmacocinética , Pirrolidinas , Compostos Radiofarmacêuticos , Receptores de Dopamina D2/metabolismo , Adulto , Antipsicóticos/efeitos adversos , Doenças dos Gânglios da Base/induzido quimicamente , Doenças dos Gânglios da Base/epidemiologia , Benzodiazepinas , Encéfalo/diagnóstico por imagem , Química Encefálica/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Olanzapina , Pirenzepina/efeitos adversos , Transtornos Psicóticos/metabolismo , Receptores de Dopamina D2/efeitos dos fármacos , Esquizofrenia/metabolismo , Tomografia Computadorizada de Emissão de Fóton Único
20.
J Psychopharmacol ; 16(3): 200-6, 2002 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12236625

RESUMO

The aim of this investigation was to compare the degree of striatal dopamine-(D2) receptor blockade by two atypical antipsychotic drugs, risperidone and olanzapine. The percentage of D2 receptor occupancy during treatment was calculated by comparing the results of 123I-iodobenzamide SPECT with those from healthy control subjects. Twenty inpatients suffering from schizophrenia or schizoaffective psychosis according to DSM IV/ICD-10 criteria were treated with clinically recommended doses of risperidone and compared with 13 inpatients treated with up to 20 mg olanzapine. Neuroleptic dose and D2 receptor blockade correlated strongly for both risperidone (Pearson r = -0.86, p = 0.0001) and olanzapine (Pearson r = -0.77, p = 0.002). There was no significant difference between the D2 receptor occupancy of the two substances when given in the clinically recommended dose range (unpaired t-test, t = -0.112, p = 0.911).


Assuntos
Antipsicóticos/metabolismo , Corpo Estriado/metabolismo , Pirenzepina/análogos & derivados , Pirenzepina/farmacocinética , Transtornos Psicóticos/tratamento farmacológico , Receptores de Dopamina D2/metabolismo , Risperidona/farmacocinética , Esquizofrenia/tratamento farmacológico , Tomografia Computadorizada de Emissão de Fóton Único , Adulto , Idoso , Antipsicóticos/uso terapêutico , Benzamidas , Benzodiazepinas , Meios de Contraste , Corpo Estriado/diagnóstico por imagem , Antagonistas dos Receptores de Dopamina D2 , Feminino , Humanos , Radioisótopos do Iodo , Masculino , Pessoa de Meia-Idade , Olanzapina , Pirenzepina/metabolismo , Transtornos Psicóticos/diagnóstico por imagem , Pirrolidinas , Risperidona/uso terapêutico , Esquizofrenia/diagnóstico por imagem
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