RESUMO
To improve the effectiveness of boron neutron capture therapy, the possibility of stimulating boron uptake was investigated in an experimental model. B16F1 mouse melanoma cells were exposed to boronophenylalanine (BPA). The intracellular boron concentration followed Michaelis-Menten kinetics in the early incubation phase. In the late phase, cellular boron concentration was linearly related to the BPA concentration in the culture medium. Incubation with L-tyrosine before exposure to BPA (preloading) increased the intracellular boron concentration by a factor of three. It is concluded that in B16F1 cells BPA is transported by L and presumably ASC (alanine, serine, and cysteine) transport systems, and that boron uptake can be effectively stimulated by L-tyrosine preloading.
Assuntos
Compostos de Boro/farmacocinética , Boro/farmacocinética , Melanoma/metabolismo , Fenilalanina/análogos & derivados , Radiossensibilizantes/farmacocinética , Tirosina/farmacocinética , Animais , Terapia por Captura de Nêutron de Boro , Camundongos , Fenilalanina/farmacocinética , Fatores de Tempo , Células Tumorais CultivadasRESUMO
OBJECTIVES: This dose-response study was designed to test two low dose regimens of urokinase administered over a prolonged time period in patients with chronic refractory angina pectoris with respect to effects on clinical symptoms and objective variables of myocardial ischemia. BACKGROUND: Patients with severe and chronic refractory angina pectoris in end-stage coronary artery disease represent an increasing clinical problem. Favorable therapeutic effects on myocardial ischemia have been reported for long-term application of low dose urokinase. METHODS: Ninety-eight patients with chronic refractory and end-stage coronary artery disease were randomly assigned to two treatment groups: group A (49 patients) received 50,000 IU and group B (49 patients) 500,000 IU of urokinase as an intravenous bolus infection three times a week over a period of 12 weeks. Variables evaluated were number of weekly anginal events, data from ergometric exercise testing with simultaneous electrocardiographic registration, semiquantitative evaluation of Tc-99m 2-methoxy isobutyl isonitrile (MIBI) scans and rheologic variables. RESULTS: After 12 weeks of treatment, anginal symptoms (events/week) were reduced significantly in group B by 70% compared with 24% in group A (p < 0.001). Fibrinogen decreased by 3% in group A and by 33% in group B (p < 0.001). Plasma viscosity and red blood cell aggregation were reduced by 6.4% (p < 0.001) and 19.9% (p < 0.001), respectively, in group B. Objective variables of myocardial ischemia were improved significantly in group B only. No cumulation of coronary ischemic events was observed in group B. CONCLUSIONS: Long-term intermittent urokinase therapy in an applied dose of 3 X 500,000 IU/week represents an effective anti-ischemic and antianginal approach for patients with refractory angina pectoris and end-stage coronary artery disease. Apart from rheologic improvement, antithrombotic properties and plaque regression are likely anti-ischemic mechanisms.
Assuntos
Angina Pectoris/tratamento farmacológico , Doença das Coronárias/tratamento farmacológico , Ativadores de Plasminogênio/administração & dosagem , Ativador de Plasminogênio Tipo Uroquinase/administração & dosagem , Idoso , Doença Crônica , Relação Dose-Resposta a Droga , Feminino , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Método Simples-Cego , Assistência Terminal , Fatores de Tempo , Resultado do TratamentoRESUMO
Techniques such as positron-emission tomography, single-photon-emission computed tomography, functional magnetic-resonance imaging and magnetoencephalography permit the observation of biological processes in the brain in a noninvasive manner. They have yielded new insights into the biological interrelations of sensory, motor and cognitive functions, as well as into brain diseases. Combined use of these techniques may provide more information than just the sum of its constituents, and this may narrow the gap between the biological data provided by these techniques and the mental models described by clinicians, mathematicians, psychologists and philosophers.
Assuntos
Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Imageamento por Ressonância Magnética/tendências , Tomografia Computadorizada de Emissão de Fóton Único/tendências , Tomografia Computadorizada de Emissão/tendências , HumanosRESUMO
The percentage of cells in the S/G2M fraction and the cytosol deoxythymidine kinase activity (TKA) were measured in autonomously functioning thyroid adenomas (AFTA) and paranodular tissue (PNT), with special regard to the impact of the patient's serum TSH concentration on DNA synthesis. The S/G2M fraction was determined by means of DNA flow cytometry, and TKA was determined by radioenzyme assay. The S/G2M fraction of AFTA (n = 15, median; 7.1%; range, 3.2-9.2%) exceeded the S/G2M fraction of normal thyroid tissue (n = 8; median, 2.8%; range, 2.3-4.0%; P = 0.008) and in 12 of 13 AFTA was 1.2- to 2.3-fold higher than the S/G2M fraction in the corresponding PNT (median, 4.0%; range, 2.5-6.7%; P = 0.0022). TKA of AFTA (n = 15; median, 681 microIU/mg; range, 432-854 microIU/mg) exceeded TKA of normal thyroid tissue (n = 8; median, 356 microIU/mg; range, 194-426 microIU/mg; P = 0.0001) and was 1.1- to 4.2-fold increased compared with TKA activity in the corresponding PNT (median, 430 microIU/mg; range, 162-570 microIU/mg; P = 0.001). In the absence of measurable serum TSH there was a constant increase in the S/G2M fractions and the TKA in AFTA vs. those in PNT. In patients treated with methimazole with serum TSH concentrations of 0.5 mIU/L or more, the S/G2M fraction and TKA in both AFTA and PNT were significantly higher than those in untreated patients with serum TSH concentrations of 0.5 mIU/L or less. In the majority of AFTA, functional autonomy and increased DNA synthesis are concomitant phenomena. Although TSH may stimulate DNA synthesis in both AFTA and PNT, measurable serum TSH concentrations are apparently not essential for DNA synthesis.
Assuntos
Adenoma/metabolismo , DNA de Neoplasias/biossíntese , Neoplasias da Glândula Tireoide/metabolismo , Tireotropina/farmacologia , Adenoma/enzimologia , Adolescente , Adulto , Citosol/enzimologia , Feminino , Humanos , Masculino , Timidina/metabolismo , Timidina Quinase/metabolismo , Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/enzimologia , Tireotropina/metabolismoRESUMO
BACKGROUND: Conditioning processes have been proposed to play a role in the development of anxiety disorders. As yet, the neurobiologic correlates of emotional learning have not been fully understood in these patients. Accordingly, brain activity was studied in subcortical and cortical regions involved in the processing of negative affect during differential aversive classical conditioning. METHODS: Twelve patients with social phobia and 12 healthy control subjects were presented with paired conditioned (CS; neutral facial expressions) and unconditioned stimuli (US; negative odor vs unmanipulated air). Functional magnetic resonance imaging (fMRI) was utilized to examine regional cerebral activity during habituation, acquisition,a nd extinction trials. Activity was measured with echo-planar-imaging (EPI), and signal intensity in individually defined anatomic regions were analyzed. RESULTS: Subjective ratings of emotional valence to the CS indicated that behavioral conditioning occurred in both groups. The presentation of CS associated with negative odor led to signal decreases in the amygdala and hippocampus of normal subjects, whereas an opposite increased activation in both regions was observed in patients. Regional differences were not found during habituation and extinction. CONCLUSIONS: Results suggest that conditioned aversive stimuli are processed in subcortical regions, with phobic patients differing from control subjects.
Assuntos
Encéfalo/fisiopatologia , Condicionamento Clássico/fisiologia , Emoções/fisiologia , Transtornos Fóbicos/fisiopatologia , Comportamento Social , Adulto , Análise de Variância , Nível de Alerta/fisiologia , Encéfalo/metabolismo , Estudos de Casos e Controles , Extinção Psicológica/fisiologia , Expressão Facial , Habituação Psicofisiológica/fisiologia , Humanos , Sistema Límbico/metabolismo , Sistema Límbico/fisiopatologia , Imageamento por Ressonância Magnética , Masculino , Odorantes , Reconhecimento Visual de Modelos/fisiologiaRESUMO
A method to image muscarinic acetylcholine receptors (muscarinic receptors) noninvasively in human brain in vivo was developed using [123I]4-iododexetimide ([123I]IDex), [123I]4-iodolevetimide ([123I]ILev), and single photon emission computed tomography (SPECT). [123I]IDex is a high-affinity muscarinic receptor antagonist. [123I]ILev is its pharmacologically inactive enantiomer and measures nonspecific binding of [123I]IDex in vitro. Regional brain activity after tracer injection was measured in four young normal volunteers for 24 h. Regional [123I]IDex and [123I]ILev activities were correlated early after injection, but not after 1.5 h. [123I]IDex activity increased over 7-12 h in neocortex, neostriatum, and thalamus, but decreased immediately after the injection peak in cerebellum. [123I]IDex activity was highest in neostriatum, followed in rank order by neocortex, thalamus, and cerebellum. [123I]IDex activity correlated with muscarinic receptor concentrations in matching brain regions. In contrast, [123I]ILev activity decreased immediately after the injection peak in all brain regions and did not correspond to muscarinic receptor concentrations. [123I]IDex activity in neocortex and neostriatum during equilibrium was six to seven times higher than [123I]ILev activity. The data demonstrate that [123I]IDex binds specifically to muscarinic receptors in vivo, whereas [123I]ILev represents the nonspecific part of [123I]IDex binding. Subtraction of [123I]ILev from [123I]IDex images on a pixel-by-pixel basis therefore reflects specific [123I]IDex binding to muscarinic receptors. Owing to its high specific binding, [123I]IDex has the potential to measure small changes in muscarinic receptor characteristics in vivo with SPECT. The use of stereoisomerism directly to measure nonspecific binding of [123I]IDex in vivo may reduce complexity in modeling approaches to muscarinic acetylcholine receptors in human brain.
Assuntos
Encéfalo/metabolismo , Receptores Muscarínicos/química , Adulto , Encéfalo/diagnóstico por imagem , Dexetimida/análogos & derivados , Humanos , Masculino , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
Accuracy in in vivo quantitation of brain function with positron emission tomography (PET) has often been limited by partial volume effects. This limitation becomes prominent in studies of aging and degenerative brain diseases where partial volume effects vary with different degrees of atrophy. The present study describes how the actual gray matter (GM) tracer concentration can be estimated using an algorithm that relates the regional fraction of GM to partial volume effects. The regional fraction of GM was determined by magnetic resonance imaging (MRI). The procedure is designated as GM PET. In computer simulations and phantom studies, the GM PET algorithm permitted a 100% recovery of the actual tracer concentration in neocortical GM and hippocampus, irrespective of the GM volume. GM PET was applied in a test case of temporal lobe epilepsy revealing an increase in radiotracer activity in GM that was undetected in the PET image before correction for partial volume effects. In computer simulations, errors in the segmentation of GM and errors in registration of PET and MRI images resulted in less than 15% inaccuracy in the GM PET image. In conclusion, GM PET permits accurate determination of the actual radiotracer concentration in human brain GM in vivo. The method differentiates whether a change in the apparent radiotracer concentration reflects solely an alteration in GM volume or rather a change in radiotracer concentration per unit volume of GM.
Assuntos
Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética , Radioisótopos/metabolismo , Tomografia Computadorizada de Emissão , Algoritmos , Encéfalo/metabolismo , Encéfalo/patologia , Simulação por ComputadorRESUMO
We describe the implementation and validation of a combined dynamic-autoradiographic approach for measuring the regional cerebral blood flow (rCBF) with 15O-butanol. From arterial blood data sampled at a rate of 1 s and list mode data of the cerebral radioactivity accumulated over 100 s, the time shift between blood and tissue curves, the dispersion constant DC, the partition coefficient p, and the CBF were estimated by least squares fitting. Using the fit results, a pixel-by-pixel parametrization of rCBF was computed for a single 40-s (autoradiographic) 15O-butanol uptake image. The mean global CBF found in 27 healthy subjects was 49 +/- 8 ml 100 g-1 min-1. Gray and white matter rCBF were 83 +/- 20 and 16 +/- 3 ml 100 g-1 min-1, respectively, with a corresponding partition coefficient p of 0.77 +/- 0.18 and 0.77 +/- 0.29 ml/g in both compartments. The quantitative images resulted in a significantly higher gray matter rCBF than the autoradiographic images.
Assuntos
Encéfalo/diagnóstico por imagem , Butanóis , Circulação Cerebrovascular , Tomografia Computadorizada de Emissão , Adulto , Autorradiografia , Feminino , Humanos , Masculino , Modelos Cardiovasculares , Radioisótopos de OxigênioRESUMO
Single Photon Emission Computed Tomography (SPECT) is a technique used to assess physiological and biochemical processes under in vivo conditions. SPECT generates tomographic images from blood flow, glucose metabolism and receptor characteristics using radioactively labelled substances. This paper reviews the state of the art of in vivo imaging of laboratory animals in modified human and dedicated animal SPECT scanners. SPECT cameras with special collimators currently reach spatial resolutions up to 1 mm and sensitivities of about 1000 cps/MBq, allowing observation of receptor activity concentration changes in the pico-mole range. The time resolution of such cameras strongly depends on the pharmacological behaviour of the tracer and can range from several minutes to hours. Within these limits the functional characterization of many processes is possible. SPECT also offers the possibility to set up dynamic study protocols and repeated measurements of the same animal. This technique reduces the need for sacrificing animals, as was commonly practiced before the development of animal cameras. Animal SPECT gives the opportunity to monitor physiological and biochemical processes in animals in vivo, without interfering with the system under observation, and may become a valuable adjunct to the instrumentation (autoradiography, in vitro methods) of animal research.
Assuntos
Encéfalo/diagnóstico por imagem , Lagomorpha/metabolismo , Roedores/metabolismo , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Vísceras/diagnóstico por imagem , Animais , Encéfalo/anatomia & histologia , Encéfalo/metabolismo , Lagomorpha/anatomia & histologia , Receptores de Superfície Celular/metabolismo , Fluxo Sanguíneo Regional/fisiologia , Roedores/anatomia & histologia , Vísceras/anatomia & histologia , Vísceras/metabolismoRESUMO
The effect of stimulus intensity (sound pressure level, SPL) of auditory stimuli on the BOLD response in the auditory cortex was investigated in 14 young and healthy subjects, with no hearing abnormalities, using echo-planar, functional magnetic resonance imaging (fMRI) during a verbal and a non-verbal auditory discrimination task. The stimuli were presented block-wise at three different intensities: 95, 85 and 75 dB (SPL). All subjects showed fMRI signal increases in superior temporal gyrus (STG) covering primary and secondary auditory cortex. Most importantly, the spatial extent of the fMRI response in STG increased with increasing stimulus intensity. It is hypothesized that spreading of excitation is associated with the encoding of increasing stimulus intensity levels. In addition, we found bifrontal activation supposedly evoked by the auditory-articulary loop of working memory. The results presented here should assist in the design of optimal activation strategies for studying the auditory cortex with fMRI paradigms and may help in understanding intensity coding of auditory stimuli.
Assuntos
Lobo Frontal/fisiologia , Percepção Sonora/fisiologia , Imageamento por Ressonância Magnética , Analisadores Neurais/fisiologia , Lobo Temporal/fisiologia , Adulto , Análise de Variância , Córtex Auditivo/fisiologia , Discriminação Psicológica/fisiologia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Percepção da Altura Sonora/fisiologia , Percepção da Fala/fisiologiaRESUMO
In this study, we aimed to characterize commonalities and differences of activation patterns during verbal episodic memory processes across different presentation modalities (visual or auditory) and different imagery content (low or high) of the presented verbal memory items. Twelve right-handed normal male volunteers took part in the study. Each subject underwent six O-15-butanol positron emission tomography scans. In six of the subjects the verbal material was presented visually, and in six subjects auditorily. The subjects had to encode and retrieve two sets of 12 word-pair associates of high (set 1) or low (set 2) imagery content (not semantically related). The presentation of nonsense words served as reference condition. Images were analyzed with statistical parametric mapping. Conjunction analysis was used to identify commonalities, and cognitive subtraction analysis was used to identify differences. The use of conjunction analyses enabled us to identify commonly activated regions involved in episodic encoding and retrieval of verbal material irrespective of the presentation modality or the imagery content. Our results add further evidence to recent findings that bilateral prefrontal activations are important for episodic retrieval and thus the role of the left prefrontal cortex has been underestimated during episodic retrieval. Furthermore, our results support the idea of functionally segregated areas in the prefrontal cortex. Finally, our results provide strong evidence that mesial parietal cortex (precuneus) involvement is not restricted to processes involving imagery.
Assuntos
Imaginação/fisiologia , Memória/fisiologia , Córtex Pré-Frontal/fisiologia , Tomografia Computadorizada de Emissão , Aprendizagem Verbal/fisiologia , Adulto , Percepção Auditiva , Dominância Cerebral/fisiologia , Humanos , Masculino , Lobo Parietal/fisiologia , Córtex Pré-Frontal/anatomia & histologia , Córtex Pré-Frontal/diagnóstico por imagem , Percepção Visual , Testes de Associação de PalavrasRESUMO
Alertness, the most basic intensity aspect of attention, probably is a prerequisite for the more complex and capacity demanding domains of attention selectivity. Behaviorally, intrinsic alertness represents the internal (cognitive) control of wakefulness and arousal; typical tasks to assess optimal levels of intrinsic alertness are simple reaction time measurements without preceding warning stimuli. Up until now only parts of the cerebral network subserving alertness have been revealed in animal, lesion, and functional imaging studies. Here, in a 15O-butanol PET activation study in 15 right-handed young healthy male volunteers for this basic attention function we found an extended right hemisphere network including frontal (anterior cingulate-dorsolateral cortical)-inferior parietal-thalamic (pulvinar and possibly the reticular nucleus) and brainstem (ponto-mesencephalic tegmentum, possibly involving the locus coeruleus) structures, when subjects waited for and rapidly responded to a centrally presented white dot by pressing a response key with the right-hand thumb.
Assuntos
Atenção/fisiologia , Encéfalo/anatomia & histologia , Encéfalo/fisiologia , Detecção de Sinal Psicológico , Adulto , Análise de Variância , Tronco Encefálico/anatomia & histologia , Tronco Encefálico/fisiologia , Lobo Frontal/anatomia & histologia , Lobo Frontal/fisiologia , Humanos , Masculino , Rede Nervosa/anatomia & histologia , Rede Nervosa/fisiologia , Lobo Parietal/anatomia & histologia , Lobo Parietal/fisiologia , Tempo de Reação , Valores de Referência , Tálamo/anatomia & histologia , Tálamo/fisiologia , Tomografia Computadorizada de Emissão , VoluntáriosRESUMO
PURPOSE: The microdosimetric weighting function approach is used widely for beam comparison studies. The suitability of this model to predict the relative biological effectiveness (RBE) of therapeutic proton beams was studied. The RBE(alpha) (i.e., linear approximation) dependence on the type of biological end point, initial proton energy, energy spread of the input proton beam, and depth of beam penetration was investigated. METHODS AND MATERIALS: Proton transport calculations for a proton energy range from 70 to 250 MeV were performed to obtain proton energy spectra at a given depth. The corresponding microdosimetric distributions of lineal energy were calculated. To these distributions the biological response function approach was applied to calculate RBE(alpha) the biological effectiveness based on a linear dose-response relationship. The early intestinal tolerance assessed by crypt regeneration in mice and the inactivation of V79 cells were taken as biological end points. RESULTS: The RBE(alpha) values approach about 1 in the plateau region and gradually increase with the proton penetration depth. In the center of the Bragg peak, at the maximum dose delivery, the values of RBE(alpha) range from 1.1 (250-MeV beam, early intestinal tolerance in mice) to 1.9 (70-MeV beam, Chinese hamster V79 cells in G1/S phase). Distal to the Bragg peak, where only a small fraction of dose is delivered, the RBE(alpha) was found to be even higher. For modulated proton beams we found an increasing RBE(alpha) with depth in the spread-out Bragg peak (SOBP). Values up to 1.37 at the distal end of the SOBP plateau (155-MeV beam, SOBP between 5.3 and 13.2 cm) were obtained. CONCLUSION: More experimental work on the determination of microdosimetric weighting functions is needed. The results of the presented calculations indicate that for therapy planning it may be necessary to account for a depth dependence on proton RBE, especially for lower energy.
Assuntos
Prótons , Radiometria , Animais , Cricetinae , Relação Dose-Resposta à Radiação , Camundongos , Método de Monte Carlo , Eficiência Biológica Relativa , SoftwareRESUMO
This study describes assessment of brain muscarinic acetylcholinergic receptors in living mice using a single-crystal radiation detection system, the high-affinity antagonist [125I]-4-iododexetimide, and the inactive enantiomer [125I]-4-iodolevetimide. Kinetics of radioligand binding, as well as perturbation by atropine displacement, can be determined using this simple probe technique.
Assuntos
Encéfalo/metabolismo , Dexetimida/análogos & derivados , Receptores Muscarínicos/metabolismo , Animais , Atropina/farmacologia , Ligação Competitiva , Dexetimida/metabolismo , Radioisótopos do Iodo , Cinética , Masculino , Camundongos , Camundongos Endogâmicos , Ensaio Radioligante , Receptores Muscarínicos/análise , Receptores Muscarínicos/efeitos dos fármacos , Fatores de TempoRESUMO
UNLABELLED: The aim of this case study was to quantify metabolic changes in tumor tissue during and directly after external radiotherapy. METHODS: We performed six FDG-PET scans of the neck in a patient with two lymph node metastases of a papillary thyroid carcinoma and an antigranulocyte antibody scintigraphy of the same region to assess the inflammatory reaction. RESULTS: The FDG-PET scans show an initial increase of tracer uptake in both metastases after application of 6 Gy followed by a slow but constant decline with increasing radiation dose. In the deep metastasis the FDG uptake returned to the initial level after 30 Gy total dose whereas the metabolic activity in the superficial lymph node remained high, even after 60 Gy total dose. The antigranulocyte scan demonstrated an intense inflammation in the latter metastasis. CONCLUSION: There is an initial enhancement in metabolism induced by irradiation which is measureable by FDG-PET. With increasing dose, the metabolic activity declines constantly. The additional inflammatory reaction might contribute to the glucose uptake in irradiated tumors.
Assuntos
Carcinoma Papilar/diagnóstico por imagem , Carcinoma Papilar/radioterapia , Desoxiglucose/análogos & derivados , Radioisótopos de Flúor , Compostos Radiofarmacêuticos , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/radioterapia , Tomografia Computadorizada de Emissão , Idoso , Carcinoma Papilar/secundário , Fluordesoxiglucose F18 , Humanos , Inflamação , Linfonodos/diagnóstico por imagem , Linfonodos/metabolismo , Linfonodos/patologia , Metástase Linfática , Masculino , PescoçoRESUMO
UNLABELLED: Several groups have developed high-resolution PET systems and shown the feasibility of in vivo studies on small laboratory animals. In this investigation, one of these systems was validated for the performance of receptor imaging studies. For this, the radiotracer concentrations obtained in the same animals with PET and with autoradiography were quantified, and the correspondence between both methods was assessed by means of correlation analysis. METHODS: Striatal radioactivity was measured in 10 Sprague-Dawley rats after injection of 60 +/- 10 MBq of the dopamine D(2) receptor ligand (18)F-(N-methyl)benperidol in 6 time frames of 6 min each. On completion of the scans, animals were killed, and their brains were removed and sectioned using a cryostat microtome. Coronal slices were subjected to storage phosphor autoradiography with BaFBr:Eu(2+)-coated imaging plates. Striatal radioactivity was quantified in both modalities using region-of-interest analysis and activity standards. RESULTS: After partial-volume correction, the median of striatal radioactivity concentration measured with PET was 0.40 MBq/cm(3) (25th percentile, 0.32; 75th percentile, 0.44). Radioactivity concentrations determined by means of storage phosphor autoradiography amounted to 0.42 MBq/cm(3) (25th percentile, 0.24; 75th percentile, 0.51). Correlation of striatal radioactivity values yielded a Pearson correlation coefficient of 0.818 (P = 0.002). Radioactivity accumulation in Harder's glands led to an overestimation of striatal activity concentrations by approximately 5%. The median of striatal radioactivity concentration after spillover correction decreased slightly to 0.38 MBq/cm(3) (25th percentile, 0.30; 75th percentile, 0.43). Correlation of striatal radioactivity values after spillover correction yielded a Pearson correlation coefficient of 0.824 (P = 0.002). CONCLUSION: The results show a significant positive correlation between radioactivity values obtained with PET and storage phosphor autoradiography used as the gold standard. Because we applied a selective dopamine D(2) receptor radioligand and because radioactivity concentrations could be reliably quantified in the target region, we may infer that in vivo receptor binding studies will be possible in small laboratory animals.
Assuntos
Bemperidol/análogos & derivados , Dopaminérgicos , Neostriado/diagnóstico por imagem , Compostos Radiofarmacêuticos , Receptores de Dopamina D2/metabolismo , Animais , Autorradiografia , Dopaminérgicos/síntese química , Processamento de Imagem Assistida por Computador , Masculino , Neostriado/anatomia & histologia , Neostriado/metabolismo , Compostos Radiofarmacêuticos/síntese química , Ratos , Ratos Sprague-Dawley , Tomografia Computadorizada de EmissãoRESUMO
UNLABELLED: PET with 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) is used for quantifying glucose metabolism in brain and myocardium in vivo. We developed and validated a similar procedure for the quantification of the two initial steps of glucose metabolism in skeletal muscle in vivo. METHODS: The measurement protocol was first optimized by computer simulations. In addition to the accuracy in sampling plasma input and tissue time-activity curves, precise determination of the fractional blood volume, that is, the extracellular tissue volume fraction, plays a key role in correctness of the determined model constants. The optimized protocol was subsequently used to estimate transmembrane muscular glucose transport and hexokinase activity in six human subjects with normal or altered glucose utilization. PET was performed during the steady state of an euglycemic hyperinsulinemic clamp. RESULTS: A three-compartment model provides a better description of the experimental data than a two- or four-compartment model. Glucose clearance from the extracellular compartment into the skeletal muscle cell (K1) ranges from 0.024 to 0.093 mL/g/min. The intracellular glucose phosphorylation rate (k3) varies between 0.030 and 0.142 min(-1). The regional muscular glucose utilization, as calculated from the determined model parameters, lies between 10.7 and 83.3 micromol/kg/min and correlates with the whole-body glucose utilization as independently determined (R2 = 0.83; P < or = 0.01). CONCLUSION: We demonstrate by computer simulations that a three-compartment model can be used to characterize the first two steps of glucose metabolism in skeletal muscle. An optimized measurement protocol is developed and applied to experimental data. This experimental approach should be appropriate to test whether glucose transport or hexokinase activity is altered in disorders of muscular glucose utilization.
Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Fluordesoxiglucose F18 , Glucose/metabolismo , Músculos/diagnóstico por imagem , Músculos/metabolismo , Compostos Radiofarmacêuticos , Tomografia Computadorizada de Emissão , Adulto , Glicemia/análise , Índice de Massa Corporal , Interpretação Estatística de Dados , Diabetes Mellitus Tipo 2/sangue , Humanos , Insulina/sangue , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , FosforilaçãoRESUMO
UNLABELLED: Iodine-123-iodobenzamide (IBZM) is a specific antagonist of dopamine D2 receptors and usually is used to study neuropsychiatric disorders. It also has a substantial affinity for malignant melanomas. This has been attributed to specific dopamine D2 receptor binding on melanoma cells because melanocytes and dopaminergic neurons share the same ectodermal origin and are both able to produce melanin. However, IBZM binding to melanoma metastases occurs predominantly 24 hr after injection, which is much later than maximal specific D2 receptor binding is expected. Furthermore, IBZM binding is not consistent in melanoma patients. This points to another mechanism of IBZM binding to melanoma cells. The aim of this study was to characterize IBZM-binding metastatic melanoma patients clinically and histologically to shed light on the nature of this mechanism. METHODS: Twenty-one patients with proven or suspected metastases of a malignant melanoma entered this prospective study after surgical removal of the primary tumor. Whole-body scans, planar scintigrams and SPECT scans were performed 2-5 hr and 1 day after intravenous injection of 185 MBq IBZM. RESULTS: The suspected diagnosis of metastatic cancer was later confirmed in 17 patients by histology, clinical follow-up, x-ray, CT or other radiologic methods. Four patients were free of tumor tissue at the time of investigation and remained stable for 2 yr thereafter. Twelve of the 17 patients had a melanotic and 5 had an amelanotic subtype of the tumor. Iodine-123-IBZM accumulation occurred in the metastases of 10 of the 12 patients with melanotic melanoma and in 0 of the 5 patients with the amelanotic tumor type (p < 0.01; chi-square test). Furthermore, IBZM accumulation occurred in 0 of the 11 amelanotic metastases but in 20 of the 25 melanotic metastases (p < 0.001). The sensitivity is, thus, 83% for the detection of melanotic melanoma metastases on a patient basis and 80% on a lesion basis. Iodine-123-IBZM scintigraphy demonstrated one previously unknown metastasis. Six initially suspected lesions were not due to melanoma metastases and were IBZM-negative. No false-positive IBZM accumulations occurred in our patients. CONCLUSION: Iodine-123-IBZM binds to melanotic malignant melanomas with high specificity and moderate sensitivity but not to amelanotic melanomas. Our data suggest that the tracer does not bind to membrane dopamine receptors of the tumor but is built in or closely bound to intracellular melanin.
Assuntos
Benzamidas , Meios de Contraste , Radioisótopos do Iodo , Melanoma/diagnóstico por imagem , Melanoma/secundário , Pirrolidinas , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Melaninas/análise , Melanoma/química , Melanoma/cirurgia , Melanoma Amelanótico/diagnóstico por imagem , Melanoma Amelanótico/secundário , Melanoma Amelanótico/cirurgia , Pessoa de Meia-Idade , Estudos Prospectivos , Sensibilidade e Especificidade , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
We describe a patient whose primary tumor was a testicular teratocarcinoma predominantly composed of embryonal carcinoma. Before chemotherapy, the retroperitoneal metastases demonstrated heterogeneous, increased glucose metabolism as measured by 2-[18F]fluoro-2-deoxy-D-glucose and PET (FDG-PET). After chemotherapy, FDG uptake was reduced to normal values despite increased tumor volume. Histology revealed a pure mature teratoma. This observation suggests that further studies are needed to determine whether tumor differentiation of testicular teratocarcinoma metastases can be assessed by measuring glucose metabolism.
Assuntos
Carcinoma Embrionário/diagnóstico por imagem , Carcinoma Embrionário/secundário , Desoxiglucose/análogos & derivados , Radioisótopos de Flúor , Neoplasias Retroperitoneais/diagnóstico por imagem , Neoplasias Retroperitoneais/secundário , Neoplasias Testiculares , Tomografia Computadorizada de Emissão/métodos , Adulto , Carcinoma Embrionário/tratamento farmacológico , Carcinoma Embrionário/metabolismo , Desoxiglucose/farmacocinética , Radioisótopos de Flúor/farmacocinética , Fluordesoxiglucose F18 , Humanos , Masculino , Neoplasias Retroperitoneais/tratamento farmacológico , Neoplasias Retroperitoneais/metabolismo , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/metabolismoRESUMO
UNLABELLED: This study compares the uptake of the nonmetabolizable amino acid analog 3-[123I]iodo-alpha-methyltyrosine (IMT) and of [methyl-11C]-L-methionine (MET) in cerebral gliomas. METHODS: In 14 patients with cerebral gliomas, IMT uptake was measured using SPECT (10 dynamic, 4 static SPECT acquisitions) and, on the same day, MET uptake by dynamic PET. The IMT and MET data were compared with respect to tracer kinetics, tumor to brain ratios (T/B) and tumor size after converting the resolution of the PET scans to that of the SPECT scans (14 mm FWHM). RESULTS: All gliomas showed increased uptake of both tracers in relation to normal brain tissue. Visual comparison of the scans yielded no differences in tumor size and shape with both methods. IMT showed a maximal tracer uptake in brain and in tumors at about 15 min postinjection which was followed by a washout of 45.0% +/- 13.5% in gliomas (mean +/- s.d., p < 0.001, n = 10) and 35.3% +/- 5.4% in normal brain (p < 0.001, n = 10) at 60 min postinjection. MET concentration in tumor tissue or brain tissue between 15 and 60 min remained constant. T/B ratios of IMT SPECT and MET PET showed a significant correlation at 15 min postinjection (r = 0.69, n = 10, p = 0.03), a low correlation for the mean values of the scans from 15-60 min postinjection (r = 0.54, n = 14, p = 0.05) and no correlation at 60 min postinjection (r = 0.09, n = 10, n.s.). CONCLUSION: IMT and MET uptake in gliomas is similar in the early, transport dominated phase. There are some differences in tumor to brain ratios between both tracers within the first hour postinjection that are mainly caused by variable washout of IMT. Imaging of tumor extent with IMT SPECT is comparable to MET PET. Thus, amino acid SPECT using IMT is a promising tool to evaluate the biological activity and intracerebral infiltration of gliomas.