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PURPOSE: Both amino acid positron emission tomography (PET) and magnetic resonance imaging (MRI) blood volume (BV) measurements are used in suspected recurrent high-grade gliomas. We compared the separate and combined diagnostic yield of simultaneously acquired dynamic contrast-enhanced (DCE) perfusion MRI and O-(2-[18F]-fluoroethyl)-L-tyrosine ([18F]FET) PET in patients with anaplastic astrocytoma and glioblastoma following standard therapy. METHODS: A total of 76 lesions in 60 hybrid [18F]FET PET/MRI scans with DCE MRI from patients with suspected recurrence of anaplastic astrocytoma and glioblastoma were included retrospectively. BV was measured from DCE MRI employing a 2-compartment exchange model (2CXM). Diagnostic performances of maximal tumour-to-background [18F]FET uptake (TBRmax), maximal BV (BVmax) and normalised BVmax (nBVmax) were determined by ROC analysis using 6-month histopathological (n = 28) or clinical/radiographical follow-up (n = 48) as reference. Sensitivity and specificity at optimal cut-offs were determined separately for enhancing and non-enhancing lesions. RESULTS: In progressive lesions, all BV and [18F]FET metrics were higher than in non-progressive lesions. ROC analyses showed higher overall ROC AUCs for TBRmax than both BVmax and nBVmax in both lesion-wise (all lesions, p = 0.04) and in patient-wise analysis (p < 0.01). Combining TBRmax with BV metrics did not increase ROC AUC. Lesion-wise positive fraction/sensitivity/specificity at optimal cut-offs were 55%/91%/84% for TBRmax, 45%/77%/84% for BVmax and 59%/84%/72% for nBVmax. Combining TBRmax and best-performing BV cut-offs yielded lesion-wise sensitivity/specificity of 75/97%. The fraction of progressive lesions was 11% in concordant negative lesions, 33% in lesions only BV positive, 64% in lesions only [18F]FET positive and 97% in concordant positive lesions. CONCLUSION: The overall diagnostic accuracy of DCE BV imaging is good, but lower than that of [18F]FET PET. Adding DCE BV imaging did not improve the overall diagnostic accuracy of [18F]FET PET, but may improve specificity and allow better lesion-wise risk stratification than [18F]FET PET alone.
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Astrocitoma , Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/diagnóstico por imagen , Neoplasias Encefálicas/patología , Estudios Retrospectivos , Tomografía de Emisión de Positrones/métodos , Astrocitoma/diagnóstico por imagen , Tirosina/metabolismo , Imagen por Resonancia Magnética/métodos , Perfusión , Espectroscopía de Resonancia MagnéticaRESUMEN
We have previously reported that PET with 3'-deoxy-3'-18F-fluorothymidine (18F-FLT) provides a non-invasive assessment of cell proliferation in vivo in meningiomas. The purpose of this prospective study was to evaluate the potential of 18F-FLT PET in predicting subsequent tumour progression in asymptomatic meningiomas. Forty-three adult patients harbouring 46 MRI-presumed (n = 40) and residual meningiomas from previous surgery (n = 6) underwent a 60-min dynamic 18F-FLT PET scan prior to radiological surveillance. Maximum and mean tumour-to-blood ratios (TBRmax, TBRmean) of tracer radioactivity were calculated. Tumour progression was defined according to the latest published trial end-point criteria for bidimensional (2D) and corresponding yet exploratory volumetric measurements from the Response Assessment of Neuro-Oncology (RANO) workgroup. Independent-sample t-test, Pearson correlation coefficient, Cox regression, and receiver operating characteristic (ROC) curve analyses were used whenever appropriate. The median follow-up time after 18F-FLT PET imaging was 18 months (range 5-33.5 months). A high concordance rate (91%) was found with regard to disease progression using 2D-RANO (n = 11) versus volumetric criteria (n = 10). Using 2D-RANO criteria, 18F-FLT uptake was significantly increased in patients with progressive disease, compared to patients with stable disease (TBRmax, 5.5 ± 1.3 versus 3.6 ± 1.1, P < 0.0001; TBRmean, 3.5 ± 0.8 versus 2.4 ± 0.7, P < 0.0001). ROC analysis yielded optimal thresholds of 4.4 for TBRmax [sensitivity 82%, specificity 77%, accuracy 78%, and area under curve (AUC) 0.871; P < 0.0001] and 2.8 for TBRmean (sensitivity 82%, specificity 77%, accuracy 78%, AUC 0.848; P = 0.001) for early differentiation of patients with progressive disease from patients with stable disease. Upon excluding patients with residual meningioma or patients with stable disease with less than 12 months follow-up, the thresholds remained unchanged with similar diagnostic accuracies. Moreover, positive correlations were found between absolute and relative tumour growth rates and 18F-FLT uptake (r < 0.513, P < 0.015) that remained similar when excluding patients with residual meningioma or patients with stable disease and shorter follow-up period. Diagnostic accuracies were slightly inferior at 76% when assessing disease progression using volumetric criteria, while the thresholds remained unchanged. Multivariate analysis revealed that TBRmax was the only independent predictor of tumour progression (P < 0.046), while age, gender, baseline tumour size, tumour location, peritumoural oedema, and residual meningioma had no influence. The study reveals that 18F-FLT PET is a promising surrogate imaging biomarker for predicting subsequent tumour progression in treatment-naïve and asymptomatic residual meningiomas.
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Neoplasias Encefálicas/diagnóstico por imagen , Meningioma/diagnóstico por imagen , Tomografía de Emisión de Positrones/métodos , Adulto , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Biomarcadores de Tumor , Neoplasias Encefálicas/diagnóstico , Progresión de la Enfermedad , Femenino , Radioisótopos de Flúor , Humanos , Imagen por Resonancia Magnética , Masculino , Meningioma/diagnóstico , Persona de Mediana Edad , Imagen Multimodal , Estudios Prospectivos , Curva ROC , Radiofármacos , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: Recurrence in glioblastoma patients often occur close to the original tumour and indicates that the current treatment is inadequate for local tumour control. In this study, we explored the feasibility of using multi-modality imaging at the time of radiotherapy planning. Specifically, we aimed to identify parameters from pre-treatment PET and MRI with potential to predict tumour recurrence. MATERIALS AND METHODS: Sixteen patients were prospectively recruited and treated according to established guidelines. Multi-parametric imaging with 18F-FET PET/CT and 18F-FDG PET/MR including diffusion and dynamic contrast enhanced perfusion MRI were performed before radiotherapy. Correlations between imaging parameters were calculated. Imaging was related to the voxel-wise outcome at the time of tumour recurrence. Within the radiotherapy target, median differences of imaging parameters in recurring and non-recurring voxels were calculated for contrast-enhancing lesion (CEL), non-enhancing lesion (NEL), and normal appearing grey and white matter. Logistic regression models were created to predict the patient-specific probability of recurrence. The most important parameters were identified using standardized model coefficients. RESULTS: Significant median differences between recurring and non-recurring voxels were observed for FDG, FET, fractional anisotropy, mean diffusivity, mean transit time, extra-vascular, extra-cellular blood volume and permeability derived from scans prior to chemo-radiotherapy. Tissue-specific patterns of voxel-wise correlations were observed. The most pronounced correlations were observed for 18F-FDG- and 18F-FET-uptake in CEL and NEL. Voxel-wise modelling of recurrence probability resulted in area under the receiver operating characteristic curve of 0.77 from scans prior to therapy. Overall, FET proved to be the most important parameter for recurrence prediction. CONCLUSION: Multi-parametric imaging before radiotherapy is feasible and significant differences in imaging parameters between recurring and non-recurring voxels were observed. Combining parameters in a logistic regression model enabled patient-specific maps of recurrence probability, where 18F-FET proved to be most important. This strategy could enable risk-adapted radiotherapy planning.
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Glioblastoma/diagnóstico por imagen , Imagen por Resonancia Magnética , Tomografía Computarizada por Tomografía de Emisión de Positrones , Adulto , Anciano , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/radioterapia , Estudios de Factibilidad , Femenino , Fluorodesoxiglucosa F18 , Glioblastoma/radioterapia , Humanos , Masculino , Persona de Mediana Edad , Probabilidad , Planificación de la Radioterapia Asistida por Computador , Recurrencia , Resultado del TratamientoRESUMEN
PURPOSE: Both [(18)F]-fluoroethyltyrosine (FET) PET and blood volume (BV) MRI supplement routine T1-weighted contrast-enhanced MRI in gliomas, but whether the two modalities provide identical or complementary information is unresolved. The aims of the study were to investigate the feasibility of simultaneous structural MRI, BV MRI and FET PET of gliomas using an integrated PET/MRI scanner and to assess the spatial and quantitative agreement in tumour imaging between BV MRI and FET PET. METHODS: A total of 32 glioma patients underwent a 20-min static simultaneous PET/MRI acquisition on a Siemens mMR system 20 min after injection of 200 MBq FET. The MRI protocol included standard structural MRI and dynamic susceptibility contrast (DSC) imaging for BV measurements. Maximal relative tumour FET uptake (TBRmax) and BV (rBVmax), and Dice coefficients were calculated to assess the quantitative and spatial congruence in the tumour volumes determined by FET PET, BV MRI and contrast-enhanced MRI. RESULTS: FET volume and TBRmax were higher in BV-positive than in BV-negative scans, and both VOLBV and rBVmax were higher in FET-positive than in FET-negative scans. TBRmax and rBVmax were positively correlated (R (2) = 0.59, p < 0.001). FET and BV positivity were in agreement in only 26 of the 32 patients and in 42 of 63 lesions, and spatial congruence in the tumour volumes as assessed by the Dice coefficients was generally poor with median Dice coefficients exceeding 0.1 in less than half the patients positive on at least one modality for any pair of modalities. In 56 % of the patients susceptibility artefacts in DSC BV maps overlapped the tumour on MRI. CONCLUSION: The study demonstrated that although tumour volumes determined by BV MRI and FET PET were quantitatively correlated, their spatial congruence in a mixed population of treated glioma patients was generally poor, and the modalities did not provide the same information in this population of patients. Combined imaging of brain tumour metabolism and perfusion using hybrid PET/MR systems may provide complementary information on tumour biology, but the potential clinical value remains to be determined in future trials.
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Volumen Sanguíneo , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/fisiopatología , Imagen por Resonancia Magnética , Imagen Multimodal , Tomografía de Emisión de Positrones , Tirosina/análogos & derivados , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Estudios de Factibilidad , Glioma/diagnóstico , Glioma/metabolismo , Glioma/patología , Glioma/fisiopatología , Humanos , Estudios Retrospectivos , Factores de Tiempo , Carga TumoralRESUMEN
The criteria for headache attributed to cervical artery dissection have been changed in the new third edition of the International Classification of Headache Disorders (ICHD-III beta). We have retrospectively investigated 19 patients diagnosed from 2001 to 2006 with cervical artery dissection at onset and followed them up six months after dissection. At dissection onset 17/19 patients were classified as headache probably attributed to vascular disorder at the time of dissection using the ICHD second edition (ICHD-II) criteria. In contrast, 17/19 of patients fulfilled the ICHD-III beta criteria for Headache or facial or neck pain attributed to cervical carotid or vertebral artery dissection or Headache attributed to intracranial arterial dissection. Six months after dissection five of 19 patients still reported persistent headache attributed to dissection. The study demonstrates that the ICHD-III beta criteria for cervical artery dissection are useful for classifying patients at the first encounter. We show for the first time that persistent headache attributed to arterial dissection is frequent.
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INTRODUCTION: To investigate if perfusion measured with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can be used to differentiate radiation necrosis from tumor recurrence in patients with high-grade glioma. METHODS: The study was approved by the institutional review board and informed consent was obtained from all subjects. 19 patients were recruited following surgery and radiation therapy for glioma. Patients had contrast enhancing lesions, which during the standard MRI examination could not be exclusively determined as recurrence or radiation necrosis. DCE-MRI was used to measure cerebral blood volume (CBV), blood-brain barrier (BBB) permeability and cerebral blood flow (CBF). Subjects also underwent FDG-PET and lesions were classified as either metabolically active or inactive. Follow-up clinical MRI and lesion histology in case of additional tissue resection was used to determine whether lesions were regressing or progressing. RESULTS: Fourteen enhancing lesions could be classified as progressing (11) or regressing (three). An empirical threshold of 2.0 ml/100 g for CBV allowed detection of regressing lesions with a sensitivity of 100 % and specificity of 100 %. FDG-PET and DCE-MRI agreed in classification of tumor status in 13 out of the 16 cases where an FDG-PET classification was obtained. In two of the remaining three patients, MRI follow-up and histology was available and both indicated that the DCE-MRI answer was correct. CONCLUSION: CBV measurements using DCE-MRI may predict the status of contrast enhancing lesions and give results very similar to FDG-PET with regards to differentiation between tumor recurrence and radiation necrosis.
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Neoplasias Encefálicas/patología , Neoplasias Encefálicas/radioterapia , Glioma/patología , Glioma/radioterapia , Angiografía por Resonancia Magnética/métodos , Recurrencia Local de Neoplasia/patología , Traumatismos por Radiación/patología , Medios de Contraste , Diagnóstico Diferencial , Femenino , Gadolinio DTPA , Humanos , Masculino , Necrosis/patología , Recurrencia Local de Neoplasia/prevención & control , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Resultado del TratamientoRESUMEN
CONTEXT: Nonpharmacological strategies are increasingly used in pediatric procedures, but in pediatric MRI, sedation and general anesthesia are still commonly required. OBJECTIVES: To evaluate the effectiveness of nonpharmacological interventions in reducing use of sedation and general anesthesia in pediatric patients undergoing MRI, and to investigate effects on scan time, image quality, and anxiety. DATA SOURCES: We searched Ovid Medline, CINAHL, Embase, and CENTRAL from inception through October 10, 2022. STUDY SELECTION: We included randomized controlled trials and quasi-experimental designs comparing the effect of a nonpharmacological intervention with standard care on use of sedation or general anesthesia, scan time, image quality, or child and parental anxiety among infants (<2 years), children, and adolescents (2-18 years) undergoing MRI. DATA EXTRACTION: Standardized instruments were used to extract data and assess study quality. RESULTS: Forty-six studies were eligible for the systematic review. Limited to studies on children and adolescents, the meta-analysis included 20 studies with 33 873 patients. Intervention versus comparator analysis showed that nonpharmacological interventions were associated with reduced need for sedation and general anesthesia in the randomized control trials (risk ratio, 0.68; 95% confidence interval, 0.48-0.95; l2 = 35%) and nonrandomized studies (risk ratio, 0.58; 95% confidence interval, 0.51-0.66; l2 = 91%). The effect was largest among children aged 3 to 10 years when compared with older children and adolescents aged 11 to 18 years. LIMITATIONS: There was substantial heterogeneity among nonrandomized studies. CONCLUSIONS: Nonpharmacological interventions must be considered as standard procedure in infants, children, and adolescents undergoing MRI.
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[This corrects the article DOI: 10.1371/journal.pone.0277767.].
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The lysosomal storage disorder Fabry disease is caused by deficient or absent activity of the GLA gene enzyme α-galactosidase A. In the present study we present the molecular and biochemical data of the Danish Fabry cohort and report 20 years' (2001-2020) experience in cascade genetic screening at the Danish National Fabry Disease Center. The Danish Fabry cohort consisted of 26 families, 18 index patients (9 males and 9 females, no available data for 8 index-patients) and 97 family members with a pathogenic GLA variant identified by cascade genetic testing (30 males and 67 females). Fourteen patients (5 males and 9 females; mean age of death 47.0 and 64.8 years respectively) died during follow-up. The completeness of the Fabry patient identification in the country has resulted in a cohort of balanced genotypes according to gender (twice number of females compared to males), indicating that the cohort was not biased by referral, and further resulted in earlier diagnosis of the disease by a lower age at diagnosis in family members compared to index-patients (mean age at diagnosis: index-patients 42.2 vs. family members 26.0 years). Six previously unreported disease-causing variants in the GLA gene were discovered. The nationwide screening and registration of Fabry disease families provide a unique possibility to establish a complete cohort of Fabry patients and to advance current knowledge of this inherited rare lysosomal storage disorder.
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Enfermedad de Fabry , Masculino , Femenino , Humanos , Persona de Mediana Edad , Enfermedad de Fabry/diagnóstico , Enfermedad de Fabry/epidemiología , Enfermedad de Fabry/genética , alfa-Galactosidasa/genética , Pruebas Genéticas , Genotipo , Dinamarca/epidemiología , MutaciónRESUMEN
Imaging studies of spontaneous migraine aura have proved challenging because of the episodic and unpredictable nature of migraine attacks. Two patients with signs of acute ischemic stroke were evaluated for thrombolysis and turned out to suffer from familial hemiplegic migraine. It was possible to record the early phase of the hemiplegic aura with computed tomography with perfusion sequences and magnetic resonance imaging. We found cerebral hypoperfusion in the relevant cortical areas within the first hour after onset of aura symptoms. This report supports the concept that migraine aura across the migraine spectrum is caused by similar mechanisms. In a setting with efficient cooperation between headache and stroke neurologists, thrombolysis centers provide the set-up and opportunity to record aura symptoms at an early phase. Furthermore, in the time of ready access to acute systemic thrombolysis treatment, these cases underscore the importance of an accurate headache history, especially in younger patients.
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Isquemia Encefálica/complicaciones , Circulación Cerebrovascular , Hemiplejía/etiología , Migraña con Aura/etiología , Enfermedad Aguda , Adulto , Imagen de Difusión Tensora , Progresión de la Enfermedad , Hemiplejía/complicaciones , Hemiplejía/diagnóstico , Humanos , Imagen por Resonancia Magnética , Masculino , Migraña con Aura/complicaciones , Migraña con Aura/diagnósticoRESUMEN
PURPOSE: PET with somatostatin receptor ligand [68Ga]Ga-DOTA-D-Phe1-Tyr3-octreotide ([68Ga]Ga-DOTA-TOC) is an established method in radiotherapy planning because of the improved detection and delineation of meningioma tissue. We investigated the diagnostic accuracy of supplementary [68Ga]Ga-DOTA-TOC PET in patients with a 3-month postoperative MRI reporting gross-total resection (GTR). EXPERIMENTAL DESIGN: Thirty-seven patients with a histologically proven meningioma and GTR on postoperative MRI were prospectively referred to [68Ga]Ga-DOTA-TOC PET. Detection and volume measurements of [68Ga]Ga-DOTA-TOC-avid lesions in relation to the primary tumor site were recorded. Residual tumor in suspicious lesions suggested by [68Ga]Ga-DOTA-TOC PET was verified by (i) tumor recurrence/progression on subsequent MRI scans according to the Response Assessment of Neuro-Oncology criteria, (ii) subsequent histology, and (iii) follow-up [68Ga]Ga-DOTA-TOC PET scan. RESULTS: Twenty-three PET scans demonstrated [68Ga]Ga-DOTA-TOC-avid lesions suspicious of residual meningioma, where 18 could be verified by (i) tumor progression on subsequent MRI scans (n = 6), (ii) histologic confirmation (n = 3), and (iii) follow-up [68Ga]Ga-DOTA-TOC PET scans confirming the initial PET findings (n = 9) after an overall median follow-up time of 17 months (range, 9-35 months). In contrast, disease recurrence was seen in only 2 of 14 patients without [68Ga]Ga-DOTA-TOC-avid lesions (P < 0.0001). The sensitivity, specificity, and diagnostic accuracy of [68Ga]Ga-DOTA-TOC PET in detecting meningioma residue was 90% [95% confidence interval (CI), 67-99], 92% (95% CI, 62-100), and 90% (95% CI, 74-98; P < 0.0001), respectively. CONCLUSIONS: The majority of patients with GTR on 3-month postoperative MRI may have small unrecognized meningioma residues that can be detected using [68Ga]Ga-DOTA-TOC PET.
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Neoplasias Meníngeas/diagnóstico , Meninges/diagnóstico por imagen , Meningioma/diagnóstico , Tomografía de Emisión de Positrones/métodos , Adulto , Anciano , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Neoplasias Meníngeas/cirugía , Meninges/patología , Meninges/cirugía , Meningioma/cirugía , Persona de Mediana Edad , Clasificación del Tumor , Neoplasia Residual , Octreótido/administración & dosificación , Octreótido/análogos & derivados , Compuestos Organometálicos/administración & dosificación , Periodo Posoperatorio , Radiofármacos/administración & dosificaciónRESUMEN
Duplications and deletions of Xq26-27 including SOX3 (Xq27.1) have been associated with X-linked mental retardation and isolated growth hormone deficiency (OMIM 300123) or X-linked panhypopituitarism (OMIM 312000). Yet, pathogenic point mutations seem to be extremely rare. We report a family with three affected males with several clinical features including mild intellectual disability, microphthalmia, coloboma, hypopituitarism, facial dysmorphology and dental anomalies, including microcephaly, retrognathia and a solitary median maxillary central incisor amongst other features. Using Whole Exome Sequencing a missense variant in SOX3, NM_005634.2:c.449C>A; p.(Ser150Tyr) was identified. Segregation analysis in the family demonstrated that the variant was inherited through healthy females with its origin in the maternal grandmother showing germline mosaicism. Thus, we report one of the first cases of a pathogenic variant in SOX3 and germline mosaicism of this variant.
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Hipopituitarismo/genética , Discapacidad Intelectual Ligada al Cromosoma X/genética , Microftalmía/genética , Mutación Missense , Factores de Transcripción SOXB1/genética , Niño , Cromosomas Humanos X , Femenino , Hormona de Crecimiento Humana/deficiencia , Humanos , Hipopituitarismo/complicaciones , Hipopituitarismo/patología , Masculino , Discapacidad Intelectual Ligada al Cromosoma X/complicaciones , Discapacidad Intelectual Ligada al Cromosoma X/patología , Microftalmía/complicaciones , Microftalmía/patología , LinajeRESUMEN
UNLABELLED: Here we compare translocator protein (TSPO) imaging using 6-chloro-2-(4'-(123)I-iodophenyl)-3-(N,N-diethyl)-imidazo[1,2-a]pyridine-3-acetamide SPECT ((123)I-CLINDE) and amino acid transport imaging using O-(2-(18)F-fluoroethyl)-l-tyrosine PET ((18)F-FET) and investigate whether (123)I-CLINDE is superior to (18)F-FET in predicting progression of glioblastoma multiforme (GBM) at follow-up. METHODS: Three patients with World Health Organization grade IV GBM were scanned with (123)I-CLINDE SPECT, (18)F-FET PET, and gadolinium-enhanced MR imaging. Molecular imaging data were compared with follow-up gadolinium-enhanced MR images or contrast-enhanced CT scans. RESULTS: The percentage overlap between volumes of interest (VOIs) of increased (18)F-FET uptake and (123)I-CLINDE binding was variable (12%-42%). The percentage overlap of MR imaging baseline VOIs was greater for (18)F-FET (79%-93%) than (123)I-CLINDE (15%-30%). In contrast, VOIs of increased contrast enhancement at follow-up compared with baseline overlapped to a greater extent with baseline (123)I-CLINDE VOIs than (18)F-FET VOIs (21% vs. 8% and 72% vs. 55%). CONCLUSION: Our preliminary results suggest that TSPO brain imaging in GBM may be a useful tool for predicting tumor progression at follow-up and may be less susceptible to changes in blood-brain barrier permeability than (18)F-FET. Larger studies are warranted to test the clinical potential of TSPO imaging in GBM, including presurgical planning and radiotherapy.
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Neoplasias Encefálicas/metabolismo , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , Glioblastoma/metabolismo , Receptores de GABA/metabolismo , Tomografía Computarizada de Emisión/métodos , Tirosina/análogos & derivados , Anciano , Biomarcadores de Tumor/metabolismo , Neoplasias Encefálicas/diagnóstico , Femenino , Fluorodesoxiglucosa F18/farmacocinética , Gadolinio , Glioblastoma/diagnóstico , Humanos , Interpretación de Imagen Asistida por Computador/métodos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Imagen Molecular , Radiofármacos/farmacocinética , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Distribución Tisular , Tirosina/farmacocinéticaRESUMEN
UNLABELLED: This study provides the first comprehensive quantification of translocator protein (TSPO) binding using SPECT and 6-chloro-2-(4'-(123)I-iodophenyl)-3-(N,N-diethyl)-imidazo[1,2-a]pyridine-3-acetamide ((123)I-CLINDE) in neurologic patients. (123)I-CLINDE is structurally related to well-known PET ligands such as (18)F-PBR111 and (18)F-DPA-714. METHODS: Six patients with cerebral stroke and 4 patients with glioblastoma multiforme (GBM) underwent 150-min dynamic SPECT scans with arterial blood sampling. Four of the patients were rescanned. All patients were genotyped for the rs6971 polymorphism. Volumes of interest were delineated on the individual SPECT scans and the coregistered MR images. Compartmental and graphical models using arterial input or the cerebellum as a reference region were used to quantify (123)I-CLINDE binding. RESULTS: Among the 6 models investigated, the 2-tissue-compartment model with arterial input described the time-activity data best. Time-stability analyses suggested that acquisition time should be at least 90 min. Intersubject variation in the cerebellar distribution volume (VT) was clearly related to the TSPO genotype. In the stroke patients the VT in the periinfarction zone, compared with VT in the ipsilateral cerebellum, ranged from 1.4 to 3.4, and in the GBM patients the VT in the tumor, compared with the VT in the cerebellum, ranged from 1.8 to 3.4. In areas of gadolinium extravasation, (123)I-CLINDE binding parameters were not significantly changed. Thus, (123)I-CLINDE binding does not appear to be importantly affected by blood-brain barrier disruption. CONCLUSION: As demonstrated within a group of stroke and GBM patients, (123)I-CLINDE SPECT can be used for quantitative assessment of TSPO expression in vivo. Because of the absence of a region devoid of TSPO, reference tissue models should be used with caution. The 2-tissue-compartment kinetic analysis of a 90-min dynamic scan with arterial blood sampling is recommended for the quantification of (123)I-CLINDE binding with SPECT.