RESUMEN
This prospective study investigated the effect of pharmacotherapy (PT) and cognitive behavioral therapy (CBT) on cerebral glucose metabolism in adults with obsessive-compulsive disorder (OCD). Dynamic positron emission tomography (PET) of the brain with F-18-fluorodeoxyglucose (FDG) was performed before and after treatment in 16 subjects diagnosed for OCD for at least 2 years (PT: n=7). Pre-to-post-treatment change of scaled local metabolic rate of glucose (SLMRGlc) was assessed separately in therapy responders and non-responders. Correlation was tested between SLMRGlc change and change of OCD, depression, or anxiety symptoms. SLMRGlc increased in the right caudate after successful therapy. The increase tended to correlate with the improvement of OCD symptom severity. The finding of increased local caudate activity after successful therapy is in contrast to most previous studies. Possible explanations include effects of therapy on concomitant depression symptoms and/or the large proportion of early-onset OCD in the present sample.
Asunto(s)
Encéfalo/diagnóstico por imagen , Terapia Cognitivo-Conductual , Glucosa/metabolismo , Trastorno Obsesivo Compulsivo/diagnóstico por imagen , Trastorno Obsesivo Compulsivo/terapia , Paroxetina/uso terapéutico , Adulto , Análisis de Varianza , Encéfalo/metabolismo , Mapeo Encefálico , Femenino , Fluorodesoxiglucosa F18 , Humanos , Procesamiento de Imagen Asistido por Computador , Modelos Lineales , Masculino , Persona de Mediana Edad , Trastorno Obsesivo Compulsivo/metabolismo , Estudios Prospectivos , Cintigrafía , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
OBJECTIVE: Neurofibromatosis type1 (NF1) is associated with cognitive and motor deficits whose pathogenesis is not well understood. 18F-Flurodeoxyglucose positron emission tomography (FDG PET) might be used to investigate putative functional correlates in the brain. METHODS: Whole-body FDG PET including the brain had been performed in 29 NF1 patients suspected for malignant peripheral nerve sheath tumours (20 females, nine males, age 31.2+/-11.8 years). Twenty-nine age-matched and sex-matched subjects without evidence of neurological/psychiatric disease in whom FDG PET had been performed for NF1-unrelated oncological indication served as controls. Individual brain FDG retention images were stereotactically normalized and scaled to a common median retention value within the brain. Scaled FDG retention was compared between the NF1 group and the control group on a voxel-by-voxel base using ANCOVA in SPM2 with the FDG uptake period as covariate. The corrected significance level alpha=0.05 was used. Voxel-based analysis was complemented by volume of interest (VOI)-based analysis using predefined standard VOIs. RESULTS: The voxel-based group comparison revealed a significant reduction of scaled FDG retention in the thalamus of the NF1 subjects within a cluster of 11.6 ml. There were no further significant effects, neither hypo-retention nor hyper-retention. Reduction of relative FDG retention in the thalamus in the NF1 subjects was confirmed by VOI analysis. The magnitude of the reduction was about 8%. CONCLUSIONS: The thalamus appears to be affected in adults with NF1. The observed magnitude of the reduction of scaled thalamic FDG retention in adults is smaller than previously reported in children. This may be consistent with a stabilization of the disease process with age.
Asunto(s)
Fluorodesoxiglucosa F18/farmacocinética , Neurofibromatosis 1/diagnóstico por imagen , Neurofibromatosis 1/metabolismo , Tálamo/diagnóstico por imagen , Tálamo/metabolismo , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Cintigrafía , Radiofármacos/farmacocinéticaRESUMEN
In a previous positron emission tomography (PET) study with the serotonin transporter (SERT) ligand [(11)C](+)McN5652, we found protracted reduction of the availability of the brain SERT in users of the drug ecstasy. However, the multi-linear reference tissue method for the quantification of SERT availability used in this study is prone to effects of altered levels of statistical noise that could simulate reduction of SERT. The aim of the present study was to take into account this confound by re-evaluation of the data now using a modelling approach that is rather insensitive to alterations in the level of statistical noise. A total of 116 subjects (30 current, 29 former ecstasy users, 29 drug-naive, 28 polydrug controls) in whom [(11)C](+)McN5652-PET had been performed previously were re-evaluated. The equilibrium specific-to-non-specific partition coefficient V"( 3) was obtained voxel-wise by application of the simplified reference tissue method (SRTM), which provides quite unbiased results up to rather large noise levels. Voxel-based comparisons between the groups were performed using statistical parametric mapping. V"(3) was reduced in the striatum and in the thalamus in current ecstasy users. This was confirmed by volume-of-interest-based analysis. This result suggests that the ecstasy-induced reduction of SERT availability in SERT-rich brain regions reported previously indicates reduced SERT binding potential rather than being an artifact of tracer kinetic modelling. SRTM analysis did not confirm previous findings in neocortical brain areas.
Asunto(s)
Artefactos , Encéfalo/efectos de los fármacos , Alucinógenos/farmacología , Isoquinolinas/farmacocinética , N-Metil-3,4-metilenodioxianfetamina/farmacología , Tomografía de Emisión de Positrones , Radiofármacos/farmacocinética , Proteínas de Transporte de Serotonina en la Membrana Plasmática/metabolismo , Adulto , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Radioisótopos de Carbono , Interpretación Estadística de Datos , Regulación hacia Abajo , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Modelos Biológicos , Modelos Estadísticos , Unión Proteica , Reproducibilidad de los Resultados , Distribución TisularRESUMEN
In infants, brain (18)F-FDG PET often requires sedation. To keep the sedation mild, the PET acquisition time should be kept short. Therefore, calculated attenuation correction is often preferred to measured attenuation correction. In addition, the infant should be positioned as comfortably as possible. Here, we report a case in which the infant's fist was near her head, resulting in severe artifacts when calculated attenuation correction was applied. Brain (18)F-FDG PET was performed for localization of a focus in an 11-mo-old girl with West's syndrome. After injection of 120 MBq of (18)F-FDG, a 20-min emission scan was obtained. Then, a 7-min hot transmission scan was acquired with 3 rotating (68)Ge/(68)Ga rod sources. Attenuation was corrected both by calculated attenuation correction and by measured attenuation correction using the transmission scan. Images reconstructed with calculated attenuation correction showed apparently increased (18)F-FDG uptake in the skin of the neck. The fist was not visible on the images because it was outside the reconstructed field of view. The lesion of increased (18)F-FDG uptake was not immediately recognizable as an artifact. It might have been misinterpreted as an active process, such as inflammation, in the skin. However, the lesion showed up neither on images reconstructed with measured attenuation correction nor on images without attenuation correction. Detailed analysis of each step in the calculated attenuation correction revealed that the fist caused the boundary detection algorithm to detect not the boundary of the head but a strongly extended boundary enclosing the fist and large "air areas" between the fist and the head. The result was a significant overestimation and overcorrection of attenuation, particularly in the region of skin near the fist.
Asunto(s)
Artefactos , Encéfalo/diagnóstico por imagen , Errores Diagnósticos/prevención & control , Epilepsia/diagnóstico por imagen , Fluorodesoxiglucosa F18 , Aumento de la Imagen/métodos , Tomografía de Emisión de Positrones/métodos , Femenino , Humanos , Interpretación de Imagen Asistida por Computador/métodos , Lactante , Radiofármacos , Sensibilidad y EspecificidadRESUMEN
OBJECTIVE: Fluorodeoxyglucose (FDG) positron emission tomography (PET) is increasingly used to support a diagnosis of Alzheimer's disease. The aim of the present study was to evaluate a new expert system (PALZ) for the fully automated analysis of FDG PET images for diagnosis of the disease. METHODS: The PALZ tool is based on the detection of the typical disease pattern in FDG PET images. Its potential for this task was evaluated in 22 consecutive patients with suspected Alzheimer's disease who had been graded as positive for the pattern by an experienced reader (visual analysis supported by statistical parametric mapping (SPM)), and in 18 controls. Dependence on scanner performance was assessed by variation of the spatial resolution of the PET images. RESULTS: All the Alzheimer's disease subjects were classified as pattern-positive by the PALZ tool. Fifteen controls were classified as normal. Sensitivity and specificity for differentiation of the patients with suspected Alzheimer's disease from the controls were 100% and 83%, respectively. The false positive finding in three controls most likely was caused by differences in attenuation correction between the normal data base of the PALZ tool (cold transmission scan) and the local data sets (hot transmission scan). There was only mild dependence on spatial resolution. CONCLUSIONS: The results of the present study suggest that the PALZ tool provides similar performance for the detection of the typical Alzheimer's disease pattern in FDG PET images as an experienced reader supported by SPM. The PALZ tool is fully automated, easy to use, and insensitive to the spatial resolution of the PET scanner used. Therefore, it has the potential for widespread clinical use.
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Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/diagnóstico , Fluorodesoxiglucosa F18/farmacología , Tomografía de Emisión de Positrones/métodos , Anciano , Automatización , Interpretación Estadística de Datos , Diagnóstico por Computador , Sistemas Especialistas , Femenino , Humanos , Interpretación de Imagen Asistida por Computador , Masculino , Persona de Mediana Edad , Radiografía , Radiofármacos , Programas InformáticosRESUMEN
INTRODUCTION: Imaging of the serotonergic innervation of the brain using positron emission tomography (PET) with the serotonin transporter (SERT) ligand [11C] (+)McN5652 might be affected by serotonin in the synaptic cleft if there is relevant interaction between [11C] (+)McN5652 and serotonin at the SERT. The aim of the present study therefore was to pharmacologically characterize the interaction of [11C] (+)McN5652 and serotonin at the SERT. METHODS: In vitro saturation analyses of [3H]serotonin uptake into HEK293 cells stably expressing the human SERT were performed in the absence and presence of unlabelled (+)McN5652. Data were evaluated assuming Michaelis-Menten kinetics. RESULTS: Unlabelled (+)McN5652 significantly reduced the maximal rate of serotonin transport V(max) of SERT without affecting the Michaelis-Menten constant K(M). CONCLUSIONS: This finding indicates that (+)McN5652 inhibits serotonin transport through the SERT in a noncompetitive manner. This might suggest that [11C] (+)McN5652 PET is not significantly affected by endogenous serotonin.
Asunto(s)
Isoquinolinas/farmacología , Transporte de Proteínas/efectos de los fármacos , Antagonistas de la Serotonina/farmacología , Serotonina/metabolismo , Unión Competitiva , Células Cultivadas , Humanos , Riñón/citología , Riñón/efectos de los fármacosRESUMEN
PURPOSE: Visual reading of [(123)I]IBZM SPECT scans depends on the experience of the interpreter. Therefore, semi-quantification of striatal IBZM uptake is commonly considered mandatory. However, semi-quantification is time consuming and prone to error, particularly if the volumes of interest (VOIs) are positioned manually. Therefore, the present paper proposes a new software tool ("IBZM tool") for fully automated and standardised processing, evaluation and documentation of [(123)I]IBZM SPECT scans. METHODS: The IBZM tool is an easy-to-use SPM toolbox. It includes automated procedures for realignment and summation of multiple frames (motion correction), stereotactic normalisation, scaling, VOI analysis of striatum-to-reference ratio R, classification of R and standardised display. In order to evaluate the tool, which was developed at the University of Hamburg, the tool was transferred to the University of Hannover. There it was applied to 27 well-documented subjects: eight patients with multi-system atrophy (MSA), 12 patients with Parkinson's disease (PD) and seven controls. The IBZM tool was compared with manual VOI analysis. RESULTS: The sensitivity and specificity of the IBZM tool for the differentiation of the MSA subjects from the controls were 100% and 86%, respectively. The IBZM tool provided improved statistical power compared with manual VOI analysis. CONCLUSION: The IBZM tool is an expert system for the detection of reduced striatal D(2) availability on [(123)I]IBZM SPECT scans. The standardised documentation supports visual and semi-quantitative evaluation, and it is useful for presenting the findings to the referring physician. The IBZM tool has the potential for widespread use, since it appears to be fairly independent of the performance characteristics of the particular SPECT system used. The tool is available free of charge.
Asunto(s)
Radioisótopos de Yodo , Yodobencenos , Radiofármacos , Programas Informáticos , Tomografía Computarizada de Emisión de Fotón Único/métodos , Adulto , Anciano , Encéfalo/diagnóstico por imagen , Estudios de Casos y Controles , Sistemas Especialistas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Atrofia de Múltiples Sistemas/diagnóstico por imagen , Enfermedad de Parkinson/diagnóstico por imagen , Sensibilidad y Especificidad , Tomografía Computarizada de Emisión de Fotón Único/estadística & datos numéricosRESUMEN
UNLABELLED: PET and SPECT have suggested that there is an age-related decline of up to 10% per decade in the availability of brain serotonin transporter (SERT) in healthy subjects, starting as early as the age of 20 y. The aim of the present study was to verify these findings in young subjects. METHODS: The equilibrium specific-to-nonspecific partition coefficient V''(3) of the SERT ligand (11)C-(+)McN5652 was obtained for 29 healthy subjects aged 18-33 y. V''(3) was tested for age dependence by linear regression analysis using both a volumes-of-interest approach and voxel-based statistical parametric mapping. The sex of the subject and the season of year were considered nuisance variables. RESULTS: Age had no significant effect on V''(3). The power for the detection of an age-related decline in V''(3) of the magnitude reported previously was 0.917. CONCLUSION: These findings indicate that age is not a relevant confounding factor for SERT availability as measured by (11)C-(+)McN5652 PET in healthy adults up to the age of about 35 y.
Asunto(s)
Envejecimiento/metabolismo , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Isoquinolinas/farmacocinética , Proteínas de Transporte de Serotonina en la Membrana Plasmática/metabolismo , Tomografía Computarizada de Emisión/métodos , Adolescente , Adulto , Factores de Edad , Radioisótopos de Carbono/farmacocinética , Femenino , Humanos , Aumento de la Imagen/métodos , Masculino , Tomografía de Emisión de Positrones/métodos , Radiofármacos/farmacocinética , Valores de Referencia , Antagonistas de la Serotonina/farmacocinética , Factores Sexuales , Distribución Tisular , Tomografía Computarizada de Emisión de Fotón Único/métodosRESUMEN
PURPOSE: In patients with neurofibromatosis type-1 (NF1) and malignant peripheral nerve sheath tumours (MPNSTs), survival rates are low and time to death is often less than 2 years. However, there are patients with a more favourable prognosis who develop metastases rather late or not at all. Since histopathology and tumour grading are not well correlated with prognosis, we aimed to evaluate the potential of (18)F-fluorodeoxyglucose positron emission tomography (FDG PET) for prediction of patient outcome in MPNST. METHODS: FDG PET was performed in 16 patients with NF1 and MPNSTs. Standardised uptake values (SUVs) were calculated for each tumour and correlated to tumour grade and patient outcome in terms of survival or death. RESULTS: Three patients with tumour grade II had an SUV <3. None of these patients developed metastases or died during a follow-up of 41-62 months. Thirteen patients with tumour grades II and III had an SUV >3. Only one of these patients is still alive after 20 months; the remaining 12 died within 4-33 months. SUV predicted long-term survival with an accuracy of 94%, compared with 69% for tumour grade. In Kaplan-Meier survival analysis, patients with an SUV >3 had a significantly shorter mean survival time, 13 months, than patients with an SUV <3, in whom the mean survival time was 52 months. Tumour grading did not reveal differences in survival time (15 vs 12 months). CONCLUSION: Tumour SUV obtained by FDG PET was a significant parameter for prediction of survival in NF1 patients with MPNSTs while histopathological tumour grading did not predict outcome.
Asunto(s)
Fluorodesoxiglucosa F18 , Neoplasias de la Vaina del Nervio/diagnóstico por imagen , Neoplasias de la Vaina del Nervio/mortalidad , Neurofibromatosis 1/diagnóstico por imagen , Neurofibromatosis 1/mortalidad , Tomografía de Emisión de Positrones/estadística & datos numéricos , Medición de Riesgo/métodos , Adolescente , Adulto , Comorbilidad , Femenino , Alemania/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud/métodos , Evaluación de Resultado en la Atención de Salud/estadística & datos numéricos , Tomografía de Emisión de Positrones/métodos , Pronóstico , Radiofármacos , Reproducibilidad de los Resultados , Factores de Riesgo , Sensibilidad y Especificidad , Tasa de SupervivenciaRESUMEN
PURPOSE: Animal data suggest that the synthetic drug ecstasy may damage brain serotonin neurons. Previously we reported protracted reductions in the availability of the serotonin transporter (SERT), an index of integrity of the axon terminals of brain serotonergic neurons, in SERT-rich brain regions in current human ecstasy users. Comparison of current ecstasy users and former ecstasy users yielded some evidence that this reduction might be reversible. However, participant selection effects could not be ruled out. Therefore, follow-up examinations were performed in these subjects to test the following a priori hypothesis in a prospective longitudinal design that eliminates participant selection effects to a large extent: availability of the SERT increases towards normal levels when ecstasy use is stopped, and remains unchanged or is further decreased if use is continued. METHODS: Two follow-up positron emission tomography measurements using the SERT ligand [11C](+)McN5652 were completed by 15 current and nine former ecstasy users. All subjects used illicit drugs other than ecstasy, too. The time interval between repeated measurements was about 1 year. The time course of the availability of the SERT was analysed in the following SERT-rich regions: mesencephalon, putamen, caudate and thalamus. RESULTS: Current ecstasy users showed a consistent increase in the availability of the SERT in the mesencephalon during the study (Friedman test: p = 0.010), which most likely was caused by a decrease in the intensity of ecstasy consumption (Spearman correlation coefficient -0.725, p = 0.002). Former ecstasy users showed a consistent increase in SERT availability in the thalamus (Friedman test: p = 0.006). CONCLUSION: Ecstasy-induced protracted alterations in the availability of the SERT might be reversible.
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Encéfalo/metabolismo , N-Metil-3,4-metilenodioxianfetamina/farmacología , Proteínas de Transporte de Serotonina en la Membrana Plasmática/biosíntesis , Adolescente , Adulto , Encéfalo/efectos de los fármacos , Encéfalo/patología , Femenino , Estudios de Seguimiento , Humanos , Isoquinolinas/farmacología , Masculino , Neuronas/metabolismo , Tomografía de Emisión de Positrones/métodos , Antagonistas de la Serotonina/farmacología , Proteínas de Transporte de Serotonina en la Membrana Plasmática/metabolismo , Trastornos Relacionados con Sustancias/patologíaRESUMEN
BACKGROUND AND PURPOSE: Statistical parametric mapping (SPM) gained increasing acceptance for the voxel-based statistical evaluation of brain positron emission tomography (PET) with the glucose analog 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) in patients with suspected Alzheimer's disease (AD). To increase the sensitivity for detection of local changes, individual differences of total brain FDG uptake are usually compensated for by proportional scaling. However, in cases of extensive hypometabolic areas, proportional scaling overestimates scaled uptake. This may cause significant underestimation of the extent of hypometabolic areas by the statistical test. METHODS: To detect this problem, the authors tested for hypermetabolism. In patients with no visual evidence of true focal hypermetabolism, significant clusters of hypermetabolism in the presence of extended hypometabolism were interpreted as false-positive findings, indicating relevant overestimation of scaled uptake. In this case, scaled uptake was reduced step by step until there were no more significant clusters of hypermetabolism. RESULTS: In 22 consecutive patients with suspected AD, proportional scaling resulted in relevant overestimation of scaled uptake in 9 patients. Scaled uptake had to be reduced by 11.1% +/- 5.3% in these cases to eliminate the artifacts. Adjusted scaling resulted in extension of existing and appearance of new clusters of hypometabolism. Total volume of the additional voxels with significant hypometabolism depended linearly on the extent of the additional scaling and was 202 +/- 118 mL on average. CONCLUSIONS: Adjusted scaling helps to identify characteristic metabolic patterns in patients with suspected AD. It is expected to increase specificity of FDGPET in this group of patients.
Asunto(s)
Enfermedad de Alzheimer/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Fluorodesoxiglucosa F18 , Tomografía de Emisión de Positrones , Radiofármacos , Enfermedad de Alzheimer/metabolismo , Encéfalo/metabolismo , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Persona de Mediana EdadRESUMEN
Despite all progress in molecular imaging methods, the actual number of validated new markers is still limited. The breakthrough of individual efforts is often hampered by lack of critical mass of resources. To overcome these shortcomings a "network" of multidisciplinary experts is indispensable. Focusing on cancer therapy, molecular imaging has a high potential impact in (a) early therapy monitoring and (b) prediction of therapeutic response. Novel molecular markers with high diagnostic potential reflecting apoptosis, proliferation and glucose metabolism are currently used in clinical trials for monitoring of tumor response to therapy. A further innovative approach for supporting individualized cancer therapy may be the application of radio-labelled therapeutic drugs at tracer concentrations in order to estimate their individual uptake in the tumor tissue. To meet this challenge, our group initiated a research project focusing on radio-labelling of selected molecules with proven therapeutic potential.
Asunto(s)
Oncología Médica , Neoplasias/diagnóstico , Técnicas de Diagnóstico por Radioisótopo , Humanos , Neoplasias/diagnóstico por imagen , CintigrafíaRESUMEN
OBJECTIVE: Recent functional imaging studies have reported evidence of alterations in the serotonergic system induced by 3,4-methylenedioxymethamphetamine (MDMA), or "Ecstasy." However, these studies have often been limited by small sample size, lack of tracer selectivity, unreliable assessment of MDMA doses, insufficiently matched comparison groups, or region-of-interest analysis. METHOD: Positron emission tomography (PET) using the specific serotonin transporter ligand [(11)C](+)McN5652 was performed in 117 subjects: 30 current MDMA users, 29 former MDMA users, 29 drug-naive comparison subjects, and 29 users of drugs other than MDMA (polydrug comparison subjects). Self-assessment of drug history was checked by analyzing hair samples. Local serotonin transporter availability was computed by a regularized reference tissue approach. Voxel-based comparison of serotonin transporter availability was performed using statistical parametric mapping (SPM 99). RESULTS: Serotonin transporter availability in current MDMA users was significantly reduced in the mesencephalon, thalamus, left caudate, hippocampus, occipital cortex, temporal lobes, and posterior cingulate gyrus compared with all other groups. Reduction was more pronounced in female than in male subjects. There was no significant difference of serotonin transporter availability among former MDMA users and the drug-naive and polydrug comparison subjects. A negative correlation between serotonin transporter availability and mean MDMA dose was found in occipital visual areas and in the left precentral sulcus of current MDMA users. In addition, there was a significant positive correlation between the serotonin transporter availability and the MDMA abstention period in brainstem and in the basal forebrain in all MDMA users. CONCLUSIONS: These findings support the hypothesis of MDMA-induced protracted alterations of the serotonergic system and indicate that the reduced availability of serotonin transporter, as measured by PET, might be reversible. Women appear to be more susceptible than men to MDMA-induced alterations of the serotonergic system.
Asunto(s)
Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Proteínas Portadoras/metabolismo , Glicoproteínas de Membrana/metabolismo , Proteínas de Transporte de Membrana , N-Metil-3,4-metilenodioxianfetamina/farmacología , Proteínas del Tejido Nervioso/metabolismo , Serotoninérgicos/farmacología , Trastornos Relacionados con Sustancias/metabolismo , Tomografía Computarizada de Emisión , Adulto , Encéfalo/diagnóstico por imagen , Radioisótopos de Carbono , Proteínas Portadoras/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Isoquinolinas , Masculino , Glicoproteínas de Membrana/efectos de los fármacos , N-Metil-3,4-metilenodioxianfetamina/efectos adversos , Proteínas del Tejido Nervioso/efectos de los fármacos , Serotoninérgicos/efectos adversos , Antagonistas de la Serotonina , Proteínas de Transporte de Serotonina en la Membrana Plasmática , Factores Sexuales , Trastornos Relacionados con Sustancias/diagnóstico por imagenRESUMEN
UNLABELLED: Alterations of the serotonergic system due to ecstasy consumption have been extensively documented in recent literature. However, reversibility of these neurotoxic effects still remains unclear. To address this question, PET was performed using the serotonin transporter (SERT) ligand (11)C-(+)-McN5652 in a total of 117 subjects subdivided into 4 groups: actual ecstasy users (n = 30), former ecstasy users (n = 29), drug-naive control subjects (n = 29), and subjects with abuse of psychoactive agents other than ecstasy (n = 29). METHODS: About 500 MBq (11)C-(+)-McN5652 were injected intravenously. Thirty-five scans were acquired according to a dynamic scan protocol of 90 min using a full-ring whole-body PET system. Transaxial slices were reconstructed using an iterative method. Individual brains were transformed to a template defined earlier. Distribution volume ratios (DVRs) were derived by application of a reference tissue approach for reversible binding. Gray matter of the cerebellum served as reference. SERT-rich brain regions--mesencephalon, putamen, caudate, and thalamus--were selected for the evaluation of SERT availability using volumes of interest predefined in the template. RESULTS: Compared with drug-naive control subjects, the DVR in actual ecstasy users was significantly reduced in the mesencephalon (P = 0.004) and the thalamus (P = 0.044). The DVR in former ecstasy users was very close to the DVR in drug-naive control subjects in all brain regions. The DVR in polydrug users was slightly higher than that in the drug-naive control subjects in all SERT-rich regions (not statistically significant). CONCLUSION: Our findings further support the hypothesis of ecstasy-induced protracted alterations of the SERT. In addition, they might indicate reversibility of the availability of SERT as measured by PET. However, this does not imply full reversibility of the neurotoxic effects.
Asunto(s)
Encéfalo/metabolismo , Proteínas Portadoras/metabolismo , Alucinógenos/efectos adversos , Glicoproteínas de Membrana/metabolismo , Proteínas de Transporte de Membrana , N-Metil-3,4-metilenodioxianfetamina/efectos adversos , Proteínas del Tejido Nervioso , Serotonina/metabolismo , Trastornos Relacionados con Sustancias/metabolismo , Tomografía Computarizada de Emisión , Adulto , Encéfalo/diagnóstico por imagen , Radioisótopos de Carbono , Proteínas Portadoras/efectos de los fármacos , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Isoquinolinas , Masculino , Glicoproteínas de Membrana/efectos de los fármacos , Radiofármacos , Antagonistas de la Serotonina , Proteínas de Transporte de Serotonina en la Membrana PlasmáticaRESUMEN
We report on a high-dose radioiodine therapy after injection of recombinant human thyrotropin (rhTSH) in a 61-y-old woman with compression of the spinal cord caused by metastasis of a follicular thyroid carcinoma. Fourteen years ago, the patient underwent subtotal thyroidectomy because of multinodular goiter without any histologic evidence for malignant disease, and the patient was put on thyroxine substitution (100 micro g/d). In April 2000, she developed paralysis of the right leg. Morphologic imaging revealed spinal compression caused by a space-occupying lesion within the thoracic spine. Subsequent biopsy and histology demonstrated metastasis of a follicular thyroid carcinoma. Therefore, high-dose radioiodine therapy was scheduled after 4 wk of hormone withdrawal. Within a few days of being off thyroxine, the patient's paralytic symptoms worsened rapidly. The patient was again put on thyroxine, 100 micro g/d, and high-dose radioiodine therapy under stimulation with rhTSH was performed without any side effects. The second high-dose radioiodine therapy 3 mo later, again performed under stimulation with rhTSH, showed significantly less iodine avidity, and thyroglobulin levels fell from 1,024 micro g/L to 361 micro g/L, thereby demonstrating therapeutic efficacy. Thus, rhTSH might be used as a tool not only in the diagnostic application but also in the therapeutic application of (131)I.