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2.
J Cereb Blood Flow Metab ; 19(5): 547-59, 1999 May.
Artigo em Inglês | MEDLINE | ID: mdl-10326722

RESUMO

Several algorithms have been proposed to improve positron emission tomography quantification by combining anatomical and functional information in a pixel-by-pixel correction scheme. The precision of these methods when applied to real data depends on the precision of the manifold correction steps, such as full-width half-maximum modeling, magnetic resonance imaging-positron emission tomography registration, tissue segmentation, or background activity estimation. A good understanding of the influence of these parameters thus is critical to the effective use of the algorithms. In the current article, the authors present a monodimensional model that allows a simple theoretical and experimental evaluation of correction imprecision. The authors then assess correction robustness in three dimensions with computer simulations, and evaluate the validity of regional SD as a correction performance criterion.


Assuntos
Algoritmos , Encéfalo/diagnóstico por imagem , Processamento de Imagem Assistida por Computador , Modelos Anatômicos , Modelos Neurológicos , Tomografia Computadorizada de Emissão , Artefatos , Simulação por Computador , Imagens de Fantasmas , Reprodutibilidade dos Testes
3.
J Cereb Blood Flow Metab ; 17(3): 343-55, 1997 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9119907

RESUMO

The in vivo quantification of the benzodiazepine receptor concentration in human brain using positron emission tomography (PET) and 11C-flumazenil (11C-FMZ), is usually based on a three-compartment model and on PET curves measured in a small number of large regions of interest; however, it should be interesting to estimate the receptor concentration for each pixel and to build quantified images of the receptor concentration. The main advantage is to allow screening of the receptor site localization and visual observation of the possible abnormalities. Up to now, all the methods described include complex experimental protocols, difficult to use in routine examinations. In this paper, we propose the partial-saturation approach to obtain parametric images of benzodiazepine receptor concentration and FMZ affinity. It consists of a single FMZ injection with a low specific activity, followed by Scatchard analysis. Like other parametric imaging methods, this partial-saturation approach can lead to a small percentage (< 1%) of unrealistic values in receptor-poor regions; however, it is the only method that allows receptor concentration and affinity images to be obtained from a single-injection 40-min experiment without blood sampling. We also propose a second method in which the receptor concentration map is directly deduced from the PET image acquired 5 to 10 min after a partial-saturation injection. This method assumes a known and constant FMZ affinity value but requires only very simple corrections of this PET image. It is robust (negative values are never found) and quite simple to use in routine examination of patients (no blood sampling, single injection, only 10-min experiment).


Assuntos
Química Encefálica , Flumazenil , Moduladores GABAérgicos , Proteínas do Tecido Nervoso/análise , Receptores de GABA-A/análise , Tomografia Computadorizada de Emissão , Flumazenil/administração & dosagem , Flumazenil/metabolismo , Flumazenil/farmacocinética , Moduladores GABAérgicos/administração & dosagem , Moduladores GABAérgicos/metabolismo , Moduladores GABAérgicos/farmacocinética , Humanos , Processamento de Imagem Assistida por Computador , Modelos Biológicos , Proteínas do Tecido Nervoso/metabolismo , Receptores de GABA-A/metabolismo
4.
J Cereb Blood Flow Metab ; 15(2): 284-300, 1995 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-7860662

RESUMO

A kinetic method using a multiinjection protocol, positron emission tomography (PET), and [11C]flumazenil as a specific ligand was used to study in vivo the flumazenil-benzodiazepine receptor interactions in the human brain. The model structure is composed of three compartments (plasma, free, and bound ligand) and five parameters (including the benzodiazepine receptor concentration). The arterial plasma concentration, after correction for metabolites, was used as the input function. The experimental protocol, which consisted of three injections of labeled and/or unlabeled ligand, allowed the evaluation of the five model parameters in various brain regions from a single experiment. In particular, the concentration of receptor sites available for binding (B'max) and the equilibrium dissociation constant (KDVR, VR being the volume of reaction) were estimated in five brain regions, including the pons, in which these parameters are identified for the first time (B'max = 4.7 +/- 1.7 pmol/ml and KDVR = 4.4 +/- 1.3 pmol/ml). Due to the large range of measured receptor concentrations, a linear correlation between B'max and KDVR was pointed out (r = 0.88, p < 0.0005) and was interpreted as a linear relationship between B'max and VR, the parameter KD being assumed constant. This result and its concordance with the published data are discussed. Simulation of the usual two-experiment Scatchard analysis, using the pons as a reference region, showed that the bias on the receptor concentration estimates introduced by this method is significant (from 20 to 40%) but can be corrected using an estimate of the receptor concentration in the pons. Furthermore, we propose a new experimental protocol, based on a Scatchard analysis of the PET data obtained with a partial-saturation experiment. This single-injection protocol is entirely noninvasive, and thus the estimation of the benzodiazepine receptor concentration and of the flumazenil affinity is now possible in human patients using a single 1-h experiment without blood sampling.


Assuntos
Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Flumazenil/metabolismo , Receptores de GABA-A/metabolismo , Tomografia Computadorizada de Emissão , Adulto , Simulação por Computador , Flumazenil/farmacocinética , Humanos , Ligantes , Masculino , Ponte/diagnóstico por imagem , Ponte/metabolismo
5.
J Cereb Blood Flow Metab ; 14(5): 749-62, 1994 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8063871

RESUMO

We propose a fully nonsupervised methodology dedicated to the fast registration of positron emission tomography (PET) and magnetic resonance images of the brain. First, discrete representations of the surfaces of interest (head or brain surface) are automatically extracted from both images. Then, a shape-independent surface-matching algorithm gives a rigid body transformation, which allows the transfer of information between both modalities. A three-dimensional (3D) extension of the chamfer-matching principle makes up the core of this surface-matching algorithm. The optimal transformation is inferred from the minimization of a quadratic generalized distance between discrete surfaces, taking into account between-modality differences in the localization of the segmented surfaces. The minimization process is efficiently performed via the precomputation of a 3D distance map. Validation studies using a dedicated brain-shaped phantom have shown that the maximum registration error was of the order of the PET pixel size (2 mm) for the wide variety of tested configurations. The software is routinely used today in a clinical context by the physicians of the Service Hospitalier Frédéric Joliot (> 150 registrations performed). The entire registration process requires approximately 5 min on a conventional workstation.


Assuntos
Encéfalo/anatomia & histologia , Encéfalo/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Tomografia Computadorizada de Emissão/métodos , Algoritmos , Mapeamento Encefálico , Simulação por Computador , Humanos , Modelos Estruturais
6.
J Cereb Blood Flow Metab ; 18(9): 951-9, 1998 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-9740098

RESUMO

Three-dimensional (3D) positron emission tomography (PET) is attractive for [18F]fluoro-DOPA studies, since the sensitivity improvement is maximal for radioactive sources located in central planes, which is usually the case for the human striata. However, the image quantitation in that mode must be assessed because of the nearly threefold increase in scattered coincidences. We report the results of [18F]fluoro-DOPA studies performed on six normal volunteers. Each one was scanned in the 3D and two-dimensional (2D) modes on the same tomograph. The quantitation in the 3D and 2D modes was compared for a Patlak graphical analysis with the occipital counts as the input function (Ki) and a striatooccipital ratio analysis. We find that, in 3D PET, a scatter correction is required to preserve the same quantitation as in 2D PET. When the 3D data sets are corrected for scatter, the quantitation of the [18F]fluoro-DOPA uptake, using the Patlak analysis, is similar in the 2D and 3D acquisition modes. Conversely, analysis of the striatooccipital ratio leads to higher values in 3D PET because of a better in-plane resolution. Finally, using the 3D mode, the dose injected to the subjects can be reduced by a factor greater than 1.5 without any loss in accuracy compared to the 2D mode.


Assuntos
Corpo Estriado/metabolismo , Di-Hidroxifenilalanina/análogos & derivados , Tomografia Computadorizada de Emissão/métodos , Adulto , Mapeamento Encefálico , Corpo Estriado/diagnóstico por imagem , Di-Hidroxifenilalanina/metabolismo , Humanos , Modelos Lineares , Masculino , Lobo Occipital/metabolismo , Valores de Referência , Reprodutibilidade dos Testes
7.
J Cereb Blood Flow Metab ; 13(3): 454-68, 1993 May.
Artigo em Inglês | MEDLINE | ID: mdl-8478404

RESUMO

The multi-injection modeling approach was used for the in vivo quantitation of benzodiazepine receptors in baboon brain using positron emission tomography (PET) and [11C]flumazenil (RO 15-1788) as a specific ligand. The model included three compartments (plasma, free, and bound ligand) and five parameters (including the benzodiazepine receptor concentration). The plasma concentration after correction for the metabolites was used as the input function. The experimental protocol consisted of four injections of labeled and/or unlabeled ligand. This protocol allows the evaluation, from a single experiment, of the five model parameters in various regions of interest. For example, in the temporal cortex, the concentration of receptor sites available for binding (B'max) and the equilibrium dissociation constant (Kd) were estimated to be 70 +/- 15 pmol/ml and 15.8 +/- 2.2 nM, respectively. The validity of the equilibrium approach, which is the most often used quantitation method, has been studied from simulated data calculated using these model parameters. The equilibrium approaches consist of reproducing in PET studies the experimental conditions that permit the use of the usual in vitro methods such as Scatchard analysis. These approaches are often open to criticism because of the difficulty of defining the notion of equilibrium in in vivo studies. However, it appears that the basic relation of Scatchard analysis is valid over a broader range of conditions than those normally used, such as the requirement of a constant bound/free ratio. Simulations showed that the values of the receptor concentration (B'max) and the equilibrium dissociation constant (Kd) found using Scatchard analysis are always underestimated. These simulations also suggest an explanation concerning the dependency of B'max and Kd on the time point employed for the Scatchard analysis, a phenomenon found by several authors. To conclude, we propose new protocols that allow the estimation of the B'max and Kd parameters using a Scatchard analysis but based on a protocol including only one or two injections. These protocols being entirely noninvasive, it thus becomes possible to investigate possible changes in receptor density and/or affinity in patients.


Assuntos
Encéfalo/metabolismo , Flumazenil/farmacocinética , Modelos Neurológicos , Tomografia Computadorizada de Emissão , Animais , Radioisótopos de Carbono , Simulação por Computador , Ligantes , Masculino , Concentração Osmolar , Papio , Estatística como Assunto , Fatores de Tempo
8.
J Cereb Blood Flow Metab ; 19(5): 533-46, 1999 May.
Artigo em Inglês | MEDLINE | ID: mdl-10326721

RESUMO

The multi-injection approach has been used to study in baboon the in vivo interactions between the D2 receptor sites and FLB 457, a ligand with a very high affinity for these receptors. The model structure was composed of four compartments (plasma, free ligand, and specifically and unspecifically bound ligands) and seven parameters (including the D2 receptor site density). The arterial plasma concentration, after correction for metabolites, was used as the input function. The experimental protocol, which consisted of three injections of labeled and/or unlabeled ligand, allowed the evaluation of all model parameters from a single positron emission tomography experiment. In particular, the concentration of receptor sites available for binding (B'max) and the apparent in vivo FLB 457 affinity were estimated in seven brain regions, including the cerebellum and several cortex regions, in which these parameters are estimated in vivo for the first time (B'max is estimated to be 4.0+/-1.3 pmol/mL in the thalamus and from 0.32 to 1.90 pmol/mL in the cortex). A low receptor density was found in the cerebellum (B'max = 0.39+/-0.17 pmol/mL), whereas the cerebellum is usually used as a reference region assumed to be devoid of D2 receptor sites. In spite of this very small concentration (1% of the striatal concentration), and because of the high affinity of the ligand, we demonstrated that after a tracer injection, most of the PET-measured radioactivity in the cerebellum results from the labeled ligand bound to receptor sites. The estimation of all the model parameters allowed simulations that led to a precise knowledge of the FLB 457 kinetics in all brain regions and gave the possibility of testing the equilibrium hypotheses and estimating the biases introduced by the usual simplified approaches.


Assuntos
Cerebelo/metabolismo , Pirrolidinas/metabolismo , Receptores de Dopamina D2/metabolismo , Salicilamidas/metabolismo , Animais , Circulação Cerebrovascular/fisiologia , Antagonistas de Dopamina/metabolismo , Microinjeções , Lobo Occipital/metabolismo , Papio , Tomografia Computadorizada de Emissão , Córtex Visual/metabolismo
9.
J Cereb Blood Flow Metab ; 10(5): 740-7, 1990 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-2384545

RESUMO

A graphical method of analysis applicable to ligands that bind reversibly to receptors or enzymes requiring the simultaneous measurement of plasma and tissue radioactivities for multiple times after the injection of a radiolabeled tracer is presented. It is shown that there is a time t after which a plot of integral of t0ROI(t')dt'/ROI(t) versus integral of t0Cp(t')dt'/ROI(t) (where ROI and Cp are functions of time describing the variation of tissue radioactivity and plasma radioactivity, respectively) is linear with a slope that corresponds to the steady-state space of the ligand plus the plasma volume,.Vp. For a two-compartment model, the slope is given by lambda + Vp, where lambda is the partition coefficient and the intercept is -1/[kappa 2(1 + Vp/lambda)]. For a three-compartment model, the slope is lambda(1 + Bmax/Kd) + Vp and the intercept is -[1 + Bmax/Kd)/k2 + [koff(1 + Kd/Bmax)]-1) [1 + Vp/lambda(1 + Bmax/Kd)]-1 (where Bmax represents the concentration of ligand binding sites and Kd the equilibrium dissociation constant of the ligand-binding site complex, koff (k4) the ligand-binding site dissociation constant, and k2 is the transfer constant from tissue to plasma). This graphical method provides the ratio Bmax/Kd from the slope for comparison with in vitro measures of the same parameter. It also provides an easy, rapid method for comparison of the reproducibility of repeated measures in a single subject, for longitudinal or drug intervention protocols, or for comparing experimental results between subjects. Although the linearity of this plot holds when ROI/Cp is constant, it can be shown that, for many systems, linearity is effectively reached some time before this. This analysis has been applied to data from [N-methyl-11C]-(-)-cocaine ([11C]cocaine) studies in normal human volunteers and the results are compared to the standard nonlinear least-squares analysis. The calculated value of Bmax/Kd for the high-affinity binding site for cocaine is 0.62 +/- 0.20, in agreement with literature values.


Assuntos
Encéfalo/metabolismo , Cocaína , Modelos Neurológicos , Radioisótopos de Carbono , Cocaína/farmacocinética , Humanos , Ligantes , Modelos Lineares , Receptores Dopaminérgicos/metabolismo , Tomografia Computadorizada de Emissão/métodos
10.
Am J Psychiatry ; 148(5): 621-6, 1991 May.
Artigo em Inglês | MEDLINE | ID: mdl-2018164

RESUMO

OBJECTIVE: The authors investigated changes in brain function associated with cocaine dependence and withdrawal to provide clues regarding the processes that lead to the uncontrollable self-administration of cocaine. METHOD: They measured regional brain metabolism with [18F]-fluorodeoxyglucose (FDG) and positron emission tomography in 15 outpatients with the diagnosis of cocaine abuse and 17 normal comparison subjects. Ten of the patients were studied less than 1 week after they had last had cocaine, and five were studied 2-4 weeks after withdrawal. RESULTS: Patients studied within 1 week of cocaine withdrawal but not those studied within 2-4 weeks of cocaine withdrawal had higher levels of global brain metabolism as well as higher levels of regional brain metabolism in the basal ganglia and orbitofrontal cortex than did normal subjects, probably as a consequence of less brain dopamine activity. There was also a significant relationship between the number of days since cocaine withdrawal and regional brain glucose metabolism in the orbitofrontal cortex and in the basal ganglia, and the correlations between cocaine craving and metabolic activity were significant in the prefrontal cortex and the orbitofrontal cortex. CONCLUSIONS: Although the time-dependent fall in metabolic activity suggests that the higher metabolic activity observed less than a week after cocaine withdrawal may represent a nonspecific expression of drug withdrawal, the selectivity of changes in glucose metabolism for the basal ganglia and for the orbitofrontal cortex suggests that the regional metabolic changes seen in cocaine abusers during detoxification are related to changes in brain dopamine activity.


Assuntos
Encéfalo/metabolismo , Cocaína/efeitos adversos , Glucose/metabolismo , Síndrome de Abstinência a Substâncias/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Adolescente , Adulto , Assistência Ambulatorial , Gânglios da Base/metabolismo , Desoxiglucose/análogos & derivados , Desoxiglucose/metabolismo , Dopamina/metabolismo , Fluordesoxiglucose F18 , Lobo Frontal/metabolismo , Humanos , Masculino , Lobo Occipital/metabolismo , Análise de Regressão , Síndrome de Abstinência a Substâncias/etiologia , Síndrome de Abstinência a Substâncias/metabolismo , Transtornos Relacionados ao Uso de Substâncias/metabolismo , Fatores de Tempo , Tomografia Computadorizada de Emissão
11.
Am J Psychiatry ; 147(6): 719-24, 1990 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-2343913

RESUMO

To assess the effects of chronic cocaine intoxication on dopamine receptors in human subjects, the authors evaluated [18F]N-methylspiroperidol binding using positron emission tomography in 10 cocaine abusers and 10 normal control subjects. Cocaine abusers who had been detoxified for 1 week or less showed significantly lower values for uptake of [18F]N-methylspiroperidol in striatum than the normal subjects, whereas the cocaine abusers who had been detoxified for 1 month showed values comparable to those obtained from normal subjects. The authors conclude that postsynaptic dopamine receptor availability decreases with chronic cocaine abuse but may recover after a drug-free interval.


Assuntos
Cocaína/farmacologia , Receptores Dopaminérgicos/efeitos dos fármacos , Transtornos Relacionados ao Uso de Substâncias/metabolismo , Adulto , Gânglios da Base/metabolismo , Corpo Estriado/metabolismo , Regulação para Baixo/efeitos dos fármacos , Radioisótopos de Flúor/metabolismo , Humanos , Receptores Dopaminérgicos/metabolismo , Espiperona/análogos & derivados , Espiperona/metabolismo , Transtornos Relacionados ao Uso de Substâncias/reabilitação , Tomografia Computadorizada de Emissão , Regulação para Cima/efeitos dos fármacos
12.
Neurology ; 45(3 Pt 1): 472-7, 1995 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-7898699

RESUMO

Lesions causing so-called rubral tremors frequently involve the substantia nigra or the nigrostriatal fibers, suggesting dopaminergic denervation as possibly contributory. We examined this hypothesis using PET and [18F]-fluorodopa in six patients with a contralateral tremor following a peduncular lesion. The denervation revealed by PET was even more marked than in severe parkinsonian patients. All patients showed partial to complete improvement with levodopa therapy. PET evaluation of D2-receptors with [76Br]bromolisuride showed no asymmetry of the D2 binding despite the important asymmetry of 18F-fluorodopa uptake. Our results indicate an important involvement of the nigral dopaminergic system in peduncular tremors that appears to be independent of postsynaptic dopamine receptors.


Assuntos
Lesões Encefálicas/diagnóstico por imagem , Hemorragia Cerebral/diagnóstico por imagem , Fibras Nervosas/diagnóstico por imagem , Receptores Dopaminérgicos/fisiologia , Núcleo Rubro/diagnóstico por imagem , Tremor/diagnóstico por imagem , Tremor/fisiopatologia , Adulto , Análise de Variância , Lesões Encefálicas/patologia , Lesões Encefálicas/fisiopatologia , Hemorragia Cerebral/patologia , Hemorragia Cerebral/fisiopatologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Receptores Dopaminérgicos/metabolismo , Núcleo Rubro/patologia , Núcleo Rubro/fisiopatologia , Substância Negra/diagnóstico por imagem , Substância Negra/patologia , Substância Negra/fisiopatologia , Tomografia Computadorizada de Emissão , Tremor/patologia
13.
J Nucl Med ; 37(1): 118-25, 1996 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8543980

RESUMO

UNLABELLED: In vivo quantification of receptor concentration and ligand affinity using data obtained with PET is based on the compartmental analysis of ligand-receptor interactions. There is, however, an inconsistency between the assumed homogeneity of the ligand concentration in each compartment, a basic hypothesis of the compartmental analysis, and the obvious heterogeneity of the tissue. Our goal was to study the effects of the free ligand concentration heterogeneity on the parameters describing in vivo binding reaction and to introduce the concept of reaction volume, VR, to account for that heterogeneity. METHODS: The reaction volume is defined as the volume in which the free ligand mass present in 1 ml of tissue would have uniformly distributed with the same concentration as that in the vicinity of the receptor sites. The consequence of the heterogeneity of the free ligand concentration is that the equilibrium dissociation rate constant estimated from PET data corresponds to KdVR and not to Kd alone (defined by the ratio of the dissociation over the association rate constants). As a consequence, it is proposed to estimate the reaction volume as the ratio between the equilibrium dissociation constants obtained from in vivo and in vitro data (KdVR and Kd, respectively). RESULTS: We used data obtained from studies performed with eight different molecules and found a correlation between the reaction volume and the molecule lipophilicity. This correlation can be used as a method to estimate the order of magnitude of VR from the lipophilicity which is easily accessible experimentally. CONCLUSION: Reaction volume is an important parameter in in vivo ligand-receptor interaction modeling.


Assuntos
Ligantes , Receptores de Superfície Celular/análise , Tomografia Computadorizada de Emissão , Animais , Humanos , Modelos Biológicos
14.
J Nucl Med ; 34(6): 981-91, 1993 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-8509869

RESUMO

The potential for noninvasive quantification of myocardial muscarinic receptors using PET data, a mathematical model, multi-injection protocols and 11C-labeled methylquinuclidinyl benzilate (MQNB) as a radioligand was previously demonstrated in dogs. The present study examines the possibility of optimizing the experimental protocol to make this approach suitable for human studies. For six normal subjects, the protocol included three injections: a tracer injection, followed 30 min later by an injection of an excess of unlabeled MQNB (displacement) and then 30 min later by a simultaneous injection of unlabeled and labeled MQNB (coinjection). The model input function was estimated from the PET data corresponding to the left ventricular cavity. This protocol enables a separate evaluation of all parameters of a ligand-receptor model which includes three compartments and seven parameters. The complexity of this three-injection protocol, however, appears to be inconvenient for clinical use. A simplified two-injection protocol (tracer injection and coinjection) was evaluated in five other normal subjects and the results were compared to those obtained with the three-injection protocol. In regions of interest over the left ventricle, the mean value of the receptor concentration B'max and the equilibrium dissociation constant Kd were 26 +/- 7 pmole/ml tissue and 2.0 +/- 0.5 pmole/ml tissue, respectively. The possible existence of nonspecific binding was studied in two subjects using a double-displacement protocol. The corresponding rate constant was found to be very low (0.03 min-1).


Assuntos
Coração/diagnóstico por imagem , Processamento de Imagem Assistida por Computador , Miocárdio/química , Receptores Muscarínicos/análise , Tomografia Computadorizada de Emissão , Adulto , Radioisótopos de Carbono , Simulação por Computador , Humanos , Modelos Teóricos , Parassimpatolíticos , Quinuclidinil Benzilato/análogos & derivados , Fatores de Tempo
15.
J Nucl Med ; 37(1): 5-11, 1996 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8544001

RESUMO

UNLABELLED: The in vivo quantification of the benzodiazepine receptor concentration in humans using PET and flumazenil (FMZ) is usually based on Scatchard analysis when the goal is to avoid blood sampling. The experimental protocols, however, include several (at least two) experiments with various specific activities in the same subject to obtain a range of bound ligand concentrations. METHODS: We propose the partial saturation method, which is based on a natural decrease in bound ligand concentration after an FMZ injection with an average dose between a tracer dose and a saturation dose. An adequate range of bound ligand concentrations can thus be obtained from a single experiment. The free ligand concentration is estimated from the PET measurement in the pons after correction for the effect of the small receptor site concentration in this reference region. RESULTS: The receptor concentration and affinity estimates obtained with this approach in six regions of interest agree with previously published values obtained by using more complex approaches. Receptor concentration appears to be insensitive to the uncertainties with regard to the receptor site concentration in the pons. CONCLUSION: The partial saturation protocol can be used to estimate both the benzodiazepine receptor concentration and the FMZ affinity in routine examinations in adults (or even in children) using a single 40-min experiment without blood sampling.


Assuntos
Encéfalo/diagnóstico por imagem , Flumazenil , Receptores de GABA-A/análise , Tomografia Computadorizada de Emissão/métodos , Adulto , Encéfalo/metabolismo , Radioisótopos de Carbono , Simulação por Computador , Flumazenil/farmacocinética , Humanos , Ligantes , Ponte/diagnóstico por imagem , Ponte/metabolismo , Fatores de Tempo
16.
J Nucl Med ; 34(11): 1899-904, 1993 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-8229231

RESUMO

This study compared positron emission tomography (PET) using oxygen-15-labeled water for measurement of coronary reserve with intracoronary Doppler in patients with left anterior descending artery stenosis and patients with no coronary lesion and a coronary reserve 3 as assessed by the invasive technique. To determine whether PET measurement of coronary reserve is altered by partial volume effect, patients with left ventricular dysfunction due to idiopathic cardiomyopathy were studied with both techniques. Direct ultrasonic measurement of coronary reserve was performed the day prior to the PET study: a Doppler catheter was placed in the proximal left anterior descending artery; mean velocity was recorded at baseline and after dipyridamole administration. Using a time-of-flight PET system, patients underwent: (1) an intravenous bolus of oxygen-15-labeled water at baseline and 4 to 6 min after intravenous infusion of dipyridamole using the same protocol as for Doppler study and (2) a 18F-fluorodeoxyglucose (FDG) myocardial imaging. Oxygen-15 time-activity curves were recorded in myocardial regions of interest (ROIs) drawn on a static FDG image. Using the left ventricular time-activity curve as an input function, a standard model with a single-tissue compartment was fitted to the PET data; myocardial blood flow was estimated as the blood-to-tissue transfer rate constant. Coronary reserve measured by PET was well correlated with the measured by intracoronary Doppler (r = 0.98, p < 0.001 for global population). This PET method is an accurate and reliable tool to noninvasively measure coronary reserve in patients, even in those with left ventricular dysfunction.


Assuntos
Circulação Coronária , Vasos Coronários/diagnóstico por imagem , Radioisótopos de Oxigênio , Tomografia Computadorizada de Emissão , Velocidade do Fluxo Sanguíneo , Pressão Sanguínea/efeitos dos fármacos , Cardiomiopatia Dilatada/diagnóstico por imagem , Cardiomiopatia Dilatada/fisiopatologia , Desoxiglucose/análogos & derivados , Dipiridamol/farmacologia , Fluordesoxiglucose F18 , Frequência Cardíaca/efeitos dos fármacos , Humanos , Pessoa de Meia-Idade , Isquemia Miocárdica/diagnóstico por imagem , Isquemia Miocárdica/fisiopatologia , Ultrassonografia , Água
17.
J Nucl Med ; 34(10): 1739-44, 1993 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-8410291

RESUMO

Iodine-123-metaiodobenzylguanidine (MIBG) is used to qualitatively assess heart innervation with single-photon emission computed tomography (SPECT). This approach is clinically useful in the prognostic evaluation of congestive heart failure. To improve quantification of uptake of the tracer using positron emission tomography (PET), we studied the characteristics of the bromoanalog of MIBG. Bromine-76-metabromobenzylguanidine (76Br-MBBG) was prepared from a heteroisotopic exchange between radioactive bromine atoms (noncarrier-added (76Br) BrNH4) and the cold iodine atoms of the precursor metaiodobenzylguanidine. Biodistribution was studied in rats and PET cardiac imaging performed in dogs. Myocardial uptake was high and prolonged in both species (mean half-life in dogs: 580 min). In rats, myocardial uptake was inhibited by desipramine by 64%, whereas after pretreatment with 6-hydroxydopamine uptake was reduced by 84%. In dogs pretreated with 6-hydroxydopamine or with desipramine, a steep washout of the tracer occurred (mean half-life: 136 min and 118 min, respectively). The non-specific uptake plus the passive neuronal diffusion of the tracer could be estimated at about 25%-30% of the total fixation. In dogs, analysis of unchanged 76Br-MBBG in plasma showed that radiotracer metabolism was slow: 60 min after injection, 80% of the radioactivity was related to unchanged 76Br-MBBG. These preliminary findings suggest that 76Br-MBBG could be used to quantitatively assess adrenergic innervation in heart disease using PET. When combined with use of 11C-CGP 12177, cardiac adrenergic neurotransmission can be assessed.


Assuntos
Fibras Adrenérgicas/diagnóstico por imagem , Bromobenzenos , Guanidinas , Coração/diagnóstico por imagem , Coração/inervação , Tomografia Computadorizada de Emissão , 3-Iodobenzilguanidina , Animais , Bromobenzenos/farmacocinética , Desipramina/farmacologia , Cães , Feminino , Guanidinas/farmacocinética , Radioisótopos do Iodo , Iodobenzenos , Masculino , Oxidopamina/farmacologia , Ratos , Ratos Wistar , Distribuição Tecidual , Tiramina/farmacologia
18.
J Nucl Med ; 36(8): 1462-71, 1995 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-7629596

RESUMO

UNLABELLED: In vivo studies of ligand-receptor interactions with PET data are based on different approaches that provide either quantitative results (receptor density and affinity) or indices that are assumed to be correlated with the receptor concentration. The aims of this study are to obtain parametric images of benzodiazepine receptor concentration and of flumazenil affinity and to study the validity of two receptor concentration indexes. METHODS: A three-compartment ligand-receptor model, [11C]flumazenil, and experimental data obtained using a three-injection protocol in human volunteers were used to acquire parametric images. The delayed activity method and the apparent distribution volume (estimated using a two-compartment model) were also tested and their results compared with those of the multi-injection approach. RESULTS: Parametric images of receptor density, affinity and all kinetic parameters were obtained with acceptable variation coefficients. A correlation between receptor density and apparent affinity was found (r = 0.83; p < 0.0005). The correlation between receptor concentration and apparent distribution volume (estimated with three- and two-compartment models, respectively) was accessed using both a linear (the usual hypothesis) and a nonlinear correlation derived from the relationship between the receptor density and the affinity. CONCLUSION: In spite of the complexity of this protocol (three injections, a 2-hr experiment, blood sampling and a metabolite study), we showed that the multi-injection approach is suitable for parametric brain imaging. By using this approach as a reference, we deduced that the distribution volume and delayed activity images are valid methods in the usual range of the benzodiazepine receptor concentrations found in the human brain.


Assuntos
Encéfalo/diagnóstico por imagem , Radioisótopos de Carbono , Flumazenil , Receptores de GABA-A/análise , Tomografia Computadorizada de Emissão , Química Encefálica , Humanos , Masculino , Modelos Neurológicos , Ensaio Radioligante , Tomografia Computadorizada de Emissão/métodos
19.
J Nucl Med ; 33(11): 2020-3, 1992 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-1432165

RESUMO

A patient with advanced neuroblastoma who had failed chemotherapy presented with a large abdominal mass and virtually total bone marrow replacement by tumor on repeated marrow biopsies. She was considered a candidate for a Phase I 131I-3F8 radioimmunotherapy trial, (MSKCC 89-141A). As a potential aid to treatment planning, a test dose of 124I-3F8 was injected and the patient was imaged over the 72 hr postinjection using two BGO based PET scanners of different designs. Time activity curves were obtained, and the cumulated activity concentration of radiolabeled 3F8 in tumor was determined. Based on MIRD, an estimated radiation absorbed dose for 131I-3F8 was 7.55 rad/mCi, in the most antibody avid lesions. Because of low uptake and unfavorable dosimetry in some bulky tumor sites, it was decided not to treat the patient with radiolabeled antibody. Positron emission tomography of 124I-labeled antibodies can be used to measure cumulated activity or residence time in tumor for more accurate estimates of radiation absorbed tumor dose from radioiodinated antibodies and can help guide management decisions in patients who are candidates for radioimmunotherapy.


Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/radioterapia , Radioisótopos do Iodo/uso terapêutico , Neuroblastoma/diagnóstico por imagem , Neuroblastoma/radioterapia , Radioimunoterapia , Tomografia Computadorizada de Emissão , Animais , Pré-Escolar , Feminino , Humanos , Doses de Radiação
20.
J Nucl Med ; 37(9): 1557-62, 1996 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8790218

RESUMO

UNLABELLED: PET is potentially very useful for the accurate in vivo quantitation of time-varying biological distributions of radiolabeled antibodies over several days. The short half-lives of most commonly used positron-emitting nuclides make them unsuitable for this purpose. Iodine-124 is a positron emitter with a half-life of 4.2 days and appropriate chemical properties. It has not been widely used because of a complex decay scheme including several high energy gamma rays. However, measurements made under realistic conditions on several different PET scanners have shown that satisfactory imaging and quantitation can be achieved. METHODS: Whole-body and head-optimized scanners with different detectors (discrete BGO, block BGO and BaF2 time-of-flight), different septa and different correction schemes were used. Measurements of resolution, quantitative linearity and the ability to quantitatively image spheres of different sizes and activities in different background activities were made using phantoms. RESULTS: Compared with conventional PET nuclides, resolution and quantitation were only slightly degraded. Sphere detectability was also only slightly worse if imaging time was increased to compensate for the lower positron abundance. CONCLUSION: Quantitative imaging with 124I appears to be possible under realistic conditions with various PET scanners.


Assuntos
Radioisótopos do Iodo , Tomografia Computadorizada de Emissão , Meia-Vida , Humanos , Processamento de Imagem Assistida por Computador , Radioisótopos do Iodo/farmacocinética , Imagens de Fantasmas , Tomografia Computadorizada de Emissão/instrumentação , Tomografia Computadorizada de Emissão/métodos
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