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1.
Braz J Psychiatry ; 44(5): 495-506, 2022 Aug 15.
Article in English | MEDLINE | ID: mdl-36420910

ABSTRACT

OBJECTIVE: Positron emission tomography (PET) allows in vivo evaluation of molecular targets in neurodegenerative diseases, such as Alzheimer's disease. Mild cognitive impairment is an intermediate stage between normal cognition and Alzheimer-type dementia. In vivo fibrillar amyloid-beta can be detected in PET using [11C]-labeled Pittsburgh compound B (11C-PiB). In contrast, [18F]fluoro-2-deoxy-d-glucose (18F-FDG) is a neurodegeneration biomarker used to evaluate cerebral glucose metabolism, indicating neuronal injury and synaptic dysfunction. In addition, early cerebral uptake of amyloid-PET tracers can determine regional cerebral blood flow. The present study compared early-phase 11C-PiB and 18F-FDG in older adults without cognitive impairment, amnestic mild cognitive impairment, and clinical diagnosis of probable Alzheimer's disease. METHODS: We selected 90 older adults, clinically classified as healthy controls, with amnestic mild cognitive impairment, or with probable Alzheimer's disease, who underwent an 18F-FDG PET, early-phase 11C-PiB PET and magnetic resonance imaging. All participants were also classified as amyloid-positive or -negative in late-phase 11C-PiB. The data were analyzed using statistical parametric mapping. RESULTS: We found that the probable Alzheimer's disease and amnestic mild cognitive impairment group had lower early-phase 11C-PiB uptake in limbic structures than 18F-FDG uptake. The images showed significant interactions between amyloid-beta status (negative or positive). However, early-phase 11C-PiB appears to provide different information from 18F-FDG about neurodegeneration. CONCLUSIONS: Our study suggests that early-phase 11C-PiB uptake correlates with 18F-FDG, irrespective of the particular amyloid-beta status. In addition, we observed distinct regional distribution patterns between both biomarkers, reinforcing the need for more robust studies to investigate the real clinical value of early-phase amyloid-PET imaging.


Subject(s)
Alzheimer Disease , Humans , Aged , Alzheimer Disease/diagnostic imaging , Alzheimer Disease/metabolism , Fluorodeoxyglucose F18/metabolism , Carbon Radioisotopes/metabolism , Brain/diagnostic imaging , Brain/pathology , Positron-Emission Tomography/methods , Amyloid beta-Peptides
2.
Braz. J. Psychiatry (São Paulo, 1999, Impr.) ; 44(5): 495-506, Sept.-Oct. 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1403774

ABSTRACT

Objective: Positron emission tomography (PET) allows in vivo evaluation of molecular targets in neurodegenerative diseases, such as Alzheimer's disease. Mild cognitive impairment is an intermediate stage between normal cognition and Alzheimer-type dementia. In vivo fibrillar amyloid-beta can be detected in PET using [11C]-labeled Pittsburgh compound B (11C-PiB). In contrast, [18F]fluoro-2-deoxy-d-glucose (18F-FDG) is a neurodegeneration biomarker used to evaluate cerebral glucose metabolism, indicating neuronal injury and synaptic dysfunction. In addition, early cerebral uptake of amyloid-PET tracers can determine regional cerebral blood flow. The present study compared early-phase 11C-PiB and 18F-FDG in older adults without cognitive impairment, amnestic mild cognitive impairment, and clinical diagnosis of probable Alzheimer's disease. Methods: We selected 90 older adults, clinically classified as healthy controls, with amnestic mild cognitive impairment, or with probable Alzheimer's disease, who underwent an 18F-FDG PET, early-phase 11C-PiB PET and magnetic resonance imaging. All participants were also classified as amyloid-positive or -negative in late-phase 11C-PiB. The data were analyzed using statistical parametric mapping. Results: We found that the probable Alzheimer's disease and amnestic mild cognitive impairment group had lower early-phase 11C-PiB uptake in limbic structures than 18F-FDG uptake. The images showed significant interactions between amyloid-beta status (negative or positive). However, early-phase 11C-PiB appears to provide different information from 18F-FDG about neurodegeneration. Conclusions: Our study suggests that early-phase 11C-PiB uptake correlates with 18F-FDG, irrespective of the particular amyloid-beta status. In addition, we observed distinct regional distribution patterns between both biomarkers, reinforcing the need for more robust studies to investigate the real clinical value of early-phase amyloid-PET imaging.

3.
J Alzheimers Dis ; 89(1): 181-192, 2022.
Article in English | MEDLINE | ID: mdl-35871330

ABSTRACT

BACKGROUND: Previous studies of hippocampal function and volume related to episodic memory deficits in patients with amnestic mild cognitive impairment (aMCI) have produced mixed results including increased or decreased activity and volume. However, most of them have not included biomarkers, such as amyloid-ß (Aß) deposition which is the hallmark for early identification of the Alzheimer's disease continuum. OBJECTIVE: We investigated the role of Aß deposition, functional hippocampal activity and structural volume in aMCI patients and healthy elderly controls (HC) using a new functional MRI (fMRI) ecological episodic memory task. METHODS: Forty-six older adults were included, among them Aß PET PIB positive (PIB+) aMCI (N = 17), Aß PET PIB negative (PIB-) aMCI (N = 15), and HC (N = 14). Hippocampal volume and function were analyzed using Freesurfer v6.0 and FSL for news headlines episodic memory fMRI task, and logistic regression for group classification in conjunction with episodic memory task and traditional neuropsychological tests. RESULTS: The aMCI PIB+ and PIB-patients showed significantly worse performance in relation to HC in most traditional neuropsychological tests and within group difference only on story recall and the ecological episodic memory fMRI task delayed recall. The classification model reached a significant accuracy (78%) and the classification pattern characterizing the PIB+ included decreased left hippocampal function and volume, increased right hippocampal function and volume, and worse episodic memory performance differing from PIB-which showed increased left hippocampus volume. CONCLUSION: The main findings showed differential neural correlates, hippocampal volume and function during episodic memory in aMCI patients with the presence of Aß deposition.


Subject(s)
Alzheimer Disease , Amyloidosis , Cognitive Dysfunction , Memory, Episodic , Aged , Alzheimer Disease/pathology , Amyloid/metabolism , Amyloid beta-Peptides/metabolism , Amyloidosis/pathology , Hippocampus/pathology , Humans , Magnetic Resonance Imaging/methods , Neuropsychological Tests
4.
Invest Ophthalmol Vis Sci ; 63(5): 20, 2022 05 02.
Article in English | MEDLINE | ID: mdl-35579902

ABSTRACT

Purpose: To evaluate color vision changes and retinal processing of chromatic and luminance pathways in subjects with Alzheimer disease (AD) and mild cognitive impairment (MCI) compared with a matched control group and whether such changes are associated with impaired brain glucose metabolism and ß-amyloid deposition in the brain. Methods: We evaluated 13 patients with AD (72.4 ± 7.7 years), 23 patients with MCI (72.5 ± 5.5 years), and 18 controls of comparable age (P = 0.44) using Cambridge color test and the heterochromatic flicker ERG (HF-ERG). The Cambridge color test was performed using the trivector protocol to estimate the protan, deutan and tritan color confusion axes. HF-ERG responses were measured at a frequency of 12 Hz, which ERGs reflect chromatic activity, and at 36 Hz, reflecting luminance pathway. A study subsample was performed using neuropsychological assessments and positron emission tomography. Results: Patients with AD presented higher mean values indicating poorer color discrimination for protan (P = 0.04) and deutan (P = 0.001) axes compared with the controls. Along the tritan axis, both patients with AD and patients with MCI showed decreased color vision (P = 0.001 and P = 0.001) compared with controls. The analyses from the HF-ERG protocol revealed no differences between the groups (P = 0.31 and P = 0.41). Diffuse color vision loss was found in individuals with signs of neurodegeneration (protan P = 0.002, deutan P = 0.003 and tritan P = 0.01), but not in individuals with signs of ß-amyloid deposition only (protan P = 0.39, deutan P = 0.48, tritan P = 0.63), regardless of their clinical classification. Conclusions: Here, patients with AD and patients with MCI present acquired color vision deficiency that may be linked with impaired brain metabolism.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Color Vision Defects , Color Vision , Alzheimer Disease/diagnostic imaging , Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/etiology , Color Vision Defects/diagnosis , Color Vision Defects/etiology , Humans , Positron-Emission Tomography
5.
J Alzheimers Dis ; 78(1): 229-244, 2020.
Article in English | MEDLINE | ID: mdl-32986673

ABSTRACT

BACKGROUND: Studies of elderly subjects using biomarkers that are proxies for Alzheimer's disease (AD) pathology have the potential to document meaningful relationships between cognitive performance and biomarker changes along the AD continuum. OBJECTIVE: To document cognitive performance differences across distinct AD stages using a categorization based on the presence of PET-assessed amyloid-ß (Aß) burden and neurodegeneration. METHODS: Patients with mild dementia compatible with AD (n = 38) or amnestic mild cognitive impairment (aMCI; n = 43) and a cognitively unimpaired group (n = 27) underwent PET with Pittsburgh compound-B (PiB) assessing Aß aggregation (A+) and [18F]FDG-PET assessing neurodegeneration ((N)+). Cognitive performance was assessed with verbal and visual episodic memory tests and the Mini-Mental State Examination. RESULTS: The A+(N)+ subgroup (n = 32) showed decreased (p < 0.001) cognitive test scores compared to both A+(N)-(n = 18) and A-(N)-(n = 49) subjects, who presented highly similar mean cognitive scores. Despite its modest size (n = 9), the A-(N)+ subgroup showed lower (p < 0.043) verbal memory scores relative to A-(N)-subjects, and trend lower (p = 0.096) scores relative to A+(N)-subjects. Continuous Aß measures (standard uptake value ratios of PiB uptake) were correlated most significantly with visual memory scores both in the overall sample and when analyses were restricted to dementia or (N)+ subjects, but not in non-dementia or (N)-groups. CONCLUSION: These results demonstrate that significant Aß-cognition relationships are highly salient at disease stages involving neurodegeneration. The fact that findings relating Aß burden to memory performance were detected only at (N)+ stages, together with the similarity of test scores between A+(N)-and A-(N)-subjects, reinforce the view that Aß-cognition relationships during early AD stages may remain undetectable unless substantially large samples are evaluated.


Subject(s)
Amyloid beta-Peptides/metabolism , Cognitive Dysfunction/diagnostic imaging , Aged , Aged, 80 and over , Alzheimer Disease/diagnostic imaging , Aniline Compounds , Cognition , Female , Fluorodeoxyglucose F18 , Humans , Male , Memory, Episodic , Neuropsychological Tests , Positron-Emission Tomography , Thiazoles
6.
Int J Mol Sci ; 21(3)2020 Jan 31.
Article in English | MEDLINE | ID: mdl-32023985

ABSTRACT

Magnetic hyperthermia (MHT) has been shown as a promising alternative therapy for glioblastoma (GBM) treatment. This study consists of three parts: The first part evaluates the heating potential of aminosilane-coated superparamagnetic iron oxide nanoparticles (SPIONa). The second and third parts comprise the evaluation of MHT multiple applications in GBM model, either in vitro or in vivo. The obtained heating curves of SPIONa (100 nm, +20 mV) and their specific absorption rates (SAR) stablished the best therapeutic conditions for frequencies (309 kHz and 557 kHz) and magnetic field (300 Gauss), which were stablished based on three in vitro MHT application in C6 GBM cell line. The bioluminescence (BLI) signal decayed in all applications and parameters tested and 309 kHz with 300 Gauss have shown to provide the best therapeutic effect. These parameters were also established for three MHT applications in vivo, in which the decay of BLI signal correlates with reduced tumor and also with decreased tumor glucose uptake assessed by positron emission tomography (PET) images. The behavior assessment showed a slight improvement after each MHT therapy, but after three applications the motor function displayed a relevant and progressive improvement until the latest evaluation. Thus, MHT multiple applications allowed an almost total regression of the GBM tumor in vivo. However, futher evaluations after the therapy acute phase are necessary to follow the evolution or tumor total regression. BLI, positron emission tomography (PET), and spontaneous locomotion evaluation techniques were effective in longitudinally monitoring the therapeutic effects of the MHT technique.


Subject(s)
Brain Neoplasms/therapy , Glioblastoma/therapy , Hyperthermia, Induced/methods , Magnetite Nanoparticles/administration & dosage , Silanes/chemistry , Animals , Brain Neoplasms/diagnostic imaging , Cell Line, Tumor , Cell Proliferation , Cell Survival , Glioblastoma/diagnostic imaging , Humans , Magnetite Nanoparticles/chemistry , Magnetite Nanoparticles/therapeutic use , Male , Mice , Particle Size , Positron-Emission Tomography , Treatment Outcome , Xenograft Model Antitumor Assays
7.
Alzheimers Dement (Amst) ; 12(1): e12122, 2020.
Article in English | MEDLINE | ID: mdl-33426265

ABSTRACT

INTRODUCTION: Reduced cognitive reserve (CR) due to very low educational (VLE) levels may influence high dementia rates in low-middle income environments, leading to decreased cognitive resilience (RES) to Alzheimer´s disease (AD) pathology. However, in vivo findings in VLE groups confirming this prediction are lacking. METHODS: Cognitively impaired patients (with clinically defined AD dementia or amnestic mild cognitive impairment) and cognitively unimpaired older adults (n = 126) were recruited for a positron emission tomography (PET) and magnetic resonance imaging (MRI) investigation in Brazil, including 37 VLE individuals (≤5 years of education). A CR score was generated combining educational attainment and vocabulary knowledge. RES indices to AD pathology were calculated using standardized residuals from linear regression models relating current cognitive performance (episodic memory or overall cognition) to amyloid beta (Aß) burden Pittsburgh compound-B ([11C]PiB-PET). RESULTS: Aß burden was lower in VLE relative to highly-educated subjects (controlling for age, sex, and Mini-Mental Status Exam [MMSE] scores) in the overall cognitively impaired sample, and in dementia subjects when the three clinically defined groups were evaluated separately. In bivariate regression analyses for the overall sample, the RES index based on a composite cognitive score was predicted by CR, socioeconomic status, and hippocampal volume (but not white matter hyperintensities or intracranial volume [ICV]); in the multivariate model, only CR retained significance (and similar results were obtained in the Aß-positive subsample). In the multivariate model for the overall sample using the RES index based on memory performance, CR, hippocampal volume, and ICV were significant predictors, whereas only CR retained significance in Aß-positive subjects. DISCUSSION: Lower CR consistently predicted less resilience to AD pathology in older adults from a low-middle income environment.

8.
Arq Gastroenterol ; 56(1): 45-50, 2019.
Article in English | MEDLINE | ID: mdl-31141073

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) can be the last step of non-alcoholic fatty liver disease (NAFLD) evolution. Experimental models are crucial to elucidate the pathogenesis of HCC secondary to NAFLD. The 2-deoxy-2-(18F)fluoro-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) plays an important role in evaluating HCC development and progression. OBJECTIVE: To standardize the imaging method of PET/CT with 18F-FDG as an evaluation tool of the experimental model of HCC secondary to NAFLD. METHODS: Ten male Sprague-Dawley rats were fed with choline-deficient high-fat diet and diethylnitrosamine (DEN) in the drinking water for 16 weeks and then received 1 mL of saline solution (0.9%) daily by gavage for three weeks. At the 16th and 19th weeks, abdominal ultrasonography (USG) was performed. 18F-FDG PET/CT images were obtained before the beginning of experiment (week 0) and at the end (week 19). Histological and immunohistochemically analysis were also performed. RESULTS: The USG results showed a homogeneous group at the 16th week with an average of 4.6±2.74 nodules per animal. At the 19th week, PET/CT findings demonstrated an average of 8.5±3.7 nodules per animal. The mean values of SUVmed and SUVmax were 2.186±0.1698 and 3.8±1.74, respectively. The average number of nodules per animal in the histological analysis was 5.5±1.5. From all nodules, 4.6% were classified as well-differentiated HCC and 81.8% were classified as poorly-differentiated HCC. CONCLUSION: 18F-FDG PET/CT was able to evaluate the development of HCC in an experimental model of NAFLD non-invasively. From the standardization of PET/CT in this model, it is possible to use this tool in future studies to monitor, in vivo and non-invasively, the progression of HCC.


Subject(s)
Carcinoma/diagnostic imaging , Liver Neoplasms, Experimental/diagnostic imaging , Positron Emission Tomography Computed Tomography/methods , Animals , Carcinoma/pathology , Carcinoma/secondary , Disease Models, Animal , Fluorodeoxyglucose F18/administration & dosage , Liver Neoplasms, Experimental/pathology , Liver Neoplasms, Experimental/secondary , Male , Neoplasm Grading , Neoplasm Staging , Non-alcoholic Fatty Liver Disease/complications , Positron Emission Tomography Computed Tomography/standards , Prognosis , Radiopharmaceuticals/administration & dosage , Rats, Sprague-Dawley , Ultrasonography
9.
Arq. gastroenterol ; 56(1): 45-50, Jan.-Mar. 2019. tab, graf
Article in English | LILACS | ID: biblio-1001332

ABSTRACT

ABSTRACT BACKGROUND: Hepatocellular carcinoma (HCC) can be the last step of non-alcoholic fatty liver disease (NAFLD) evolution. Experimental models are crucial to elucidate the pathogenesis of HCC secondary to NAFLD. The 2-deoxy-2-(18F)fluoro-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) plays an important role in evaluating HCC development and progression. OBJECTIVE: To standardize the imaging method of PET/CT with 18F-FDG as an evaluation tool of the experimental model of HCC secondary to NAFLD. METHODS: Ten male Sprague-Dawley rats were fed with choline-deficient high-fat diet and diethylnitrosamine (DEN) in the drinking water for 16 weeks and then received 1 mL of saline solution (0.9%) daily by gavage for three weeks. At the 16th and 19th weeks, abdominal ultrasonography (USG) was performed. 18F-FDG PET/CT images were obtained before the beginning of experiment (week 0) and at the end (week 19). Histological and immunohistochemically analysis were also performed. RESULTS: The USG results showed a homogeneous group at the 16th week with an average of 4.6±2.74 nodules per animal. At the 19th week, PET/CT findings demonstrated an average of 8.5±3.7 nodules per animal. The mean values of SUVmed and SUVmax were 2.186±0.1698 and 3.8±1.74, respectively. The average number of nodules per animal in the histological analysis was 5.5±1.5. From all nodules, 4.6% were classified as well-differentiated HCC and 81.8% were classified as poorly-differentiated HCC. CONCLUSION: 18F-FDG PET/CT was able to evaluate the development of HCC in an experimental model of NAFLD non-invasively. From the standardization of PET/CT in this model, it is possible to use this tool in future studies to monitor, in vivo and non-invasively, the progression of HCC.


RESUMO BACKGROUND: O carcinoma hepatocelular (CHC) pode ser a última fase da doença hepática gordurosa não alcoólica (DHGNA). Modelos experimentais são cruciais para elucidação da patogênese do CHC secundário a DHGNA. A tomografia por emissão de pósitrons/tomografia computadorizada (PET/TC) com 2-desoxi-2-(18F)fluoro-D-glicose (18F-FDG) desempenha um importante papel na avaliação do desenvolvimento e progressão do CHC. OBJETIVO: Padronizar a metodologia de imagem por PET/TC com 18F-FDG como uma ferramenta de avaliação do modelo experimental de CHC secundário a DHGNA. MÉTODOS: Dez ratos Sprague-Dawley machos foram alimentados com dieta hiperlipídica deficiente em colina associada a dietilnitrosamina (DEN) na água de beber por 16 semanas e depois receberam 1 mL de solução salina (0,9%) por gavagem diariamente por três semanas. Nas 16ª e 19ª semanas, foi realizada a ultrassonografia abdominal. As imagens do PET/TC com 18F-FDG foram obtidas antes do início do experimento (semana 0) e no final (semana 19). Análises histológica e imunohistoquímica também foram realizadas. RESULTADOS: Os resultados da ultrassonografia demonstraram um grupo homogêneo na 16ª semana com uma média de 4,6±2,74 nódulos por animal. Na 19ª semana, os achados do PET/CT demonstraram uma média de 8,5±3,7 nódulos por animal. Os valores médios de SUVmed e SUVmáx foram 2,186±0,1698 e 3,8±1,74, respectivamente. A média do número de nódulos na análise histológica foi de 5,5±1,5. De todos os nódulos, 4,6% foram classificados como bem diferenciados e 81,8% foram classificados como CHC pouco diferenciado. CONCLUSÃO: O PET/TC com 18F-FDG foi capaz de avaliar o desenvolvimento do CHC secundário a DHGNA de forma não invasiva. A partir da padronização do PET/CT neste modelo, faz-se possível a utilização desta ferramenta em futuros estudos para monitorar, in vivo e de forma não invasiva, a progressão do CHC.


Subject(s)
Animals , Male , Carcinoma/diagnostic imaging , Positron Emission Tomography Computed Tomography/methods , Liver Neoplasms, Experimental/diagnostic imaging , Prognosis , Carcinoma/pathology , Carcinoma/secondary , Ultrasonography , Rats, Sprague-Dawley , Radiopharmaceuticals/administration & dosage , Fluorodeoxyglucose F18/administration & dosage , Disease Models, Animal , Neoplasm Grading , Non-alcoholic Fatty Liver Disease/complications , Positron Emission Tomography Computed Tomography/standards , Liver Neoplasms, Experimental/pathology , Liver Neoplasms, Experimental/secondary , Neoplasm Staging
10.
Amino Acids ; 48(3): 821-831, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26592499

ABSTRACT

Gliomas are the most common type among all central nervous system tumors. The aggressiveness of gliomas is correlated with the level of angiogenesis and is often associated with prognosis. The aim of this study is to evaluate the novel GX1 peptide and the heterodimer RGD-GX1 radiolabeled with technetium-99m, for angiogenesis detection in glioma models. Radiolabeling and radiochemical controls were assessed for both radioconjugates. In vitro binding studies in glioma tumor cells were performed, as well as biodistribution in SCID mice bearing tumor cells, in order to evaluate the biological behavior and tumor uptake of the radiocomplexes. Blocking and imaging studies were also conducted. MicroSPECT/CT images were acquired in animals with experimentally implanted intracranial tumor. Open field activity was performed to evaluate behavior, as well as perfusion and histology analysis. The radiochemical purity of both radiotracers was greater than 96 %. In vitro binding studies revealed rather similar binding profi le for each molecule. The highest binding was for RGD-GX1 peptide at 120 min in U87MG cells (1.14 ± 0.35 %). Tumor uptake was also favorable for RGD-GX1 peptide in U87MG cells, reaching 2.96 ± 0.70 % at 1 h p.i. with 47 % of blocking. Imaging studies also indicated better visualization for RGD-GX1 peptide in U87MG cells. Behavior evaluation pointed brain damage and histology studies confirmed actual tumor in the uptake site. The results with the angiogenesis seeking molecule (99m)Tc-HYNIC-E-[c(RGDfk)-c(GX1)] were successful, and better than with (99m)Tc-HYNIC-PEG4-c(GX1). Future studies targeting angiogenesis in other glioma and nonglioma tumor models are recommended.


Subject(s)
Glioma/diagnostic imaging , Neovascularization, Pathologic/diagnostic imaging , Oligopeptides/administration & dosage , Radiopharmaceuticals/administration & dosage , Animals , Cell Line, Tumor , Disease Models, Animal , Glioma/diagnosis , Glioma/metabolism , Humans , Mice , Mice, SCID , Neovascularization, Pathologic/metabolism , Oligopeptides/chemistry , Oligopeptides/metabolism , Radiopharmaceuticals/chemistry , Radiopharmaceuticals/metabolism , Technetium/administration & dosage , Technetium/chemistry , Technetium/metabolism , Tomography, Emission-Computed, Single-Photon
11.
J Neuroimmune Pharmacol ; 9(4): 468-82, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24809810

ABSTRACT

Positron emission tomography (PET) is a non-invasive technique for quantitative imaging of biochemical and physiological processes in animals and humans. PET uses probes labeled with a radioactive isotope, called PET tracers, which can bind to or be converted by a specific biological target and thus can be applied to detect and monitor different aspects of diseases. The number of applications of PET imaging in multiple sclerosis is still limited. Clinical studies using PET are basically focused on monitoring changes in glucose metabolism and the presence of activated microglia/macrophages in sclerotic lesions. In preclinical studies, PET imaging of targets for other processes, like demyelination and remyelination, has been investigated and may soon be translated to clinical applications. Moreover, more PET tracers that could be relevant for MS are available now, but have not been studied in this context yet. In this review, we summarize the PET imaging studies performed in multiple sclerosis up to now. In addition, we will identify potential applications of PET imaging of processes or targets that are of interest to MS research, but have yet remained largely unexplored.


Subject(s)
Functional Neuroimaging/trends , Glucose/metabolism , Multiple Sclerosis/diagnostic imaging , Multiple Sclerosis/pathology , Positron-Emission Tomography/trends , Animals , Brain/metabolism , Brain/physiology , Functional Neuroimaging/methods , Humans , Multiple Sclerosis/metabolism , Multiple Sclerosis/physiopathology , Myelin Sheath/physiology , Nerve Degeneration/physiopathology , Positron-Emission Tomography/methods , Radioactive Tracers , Receptors, GABA/metabolism , Receptors, Purinergic P1/metabolism
12.
Eur J Nucl Med Mol Imaging ; 41(5): 995-1003, 2014 May.
Article in English | MEDLINE | ID: mdl-24499866

ABSTRACT

PURPOSE: In this study, we compared the ability of [(11)C]CIC, [(11)C]MeDAS and [(11)C]PIB to reveal temporal changes in myelin content in focal lesions in the lysolecithin rat model of multiple sclerosis. Pharmacokinetic modelling was performed to determine the best method to quantify tracer uptake. METHODS: Sprague-Dawley rats were stereotactically injected with either 1 % lysolecithin or saline into the corpus callosum and striatum of the right brain hemisphere. Dynamic PET imaging with simultaneous arterial blood sampling was performed 7 days after saline injection (control group), 7 days after lysolecithin injection (demyelination group) and 4 weeks after lysolecithin injection (remyelination group). RESULTS: The kinetics of [(11)C]CIC, [(11)C]MeDAS and [(11)C]PIB was best fitted by Logan graphical analysis, suggesting that tracer binding is reversible. Compartment modelling revealed that all tracers were fitted best with the reversible two-tissue compartment model. Tracer uptake and distribution volume in lesions were in agreement with myelin status. However, the slow kinetics and homogeneous brain uptake of [(11)C]CIC make this tracer less suitable for in vivo PET imaging. [(11)C]PIB showed good uptake in the white matter in the cerebrum, but [(11)C]PIB uptake in the cerebellum was low, despite high myelin density in this region. [(11)C]MeDAS distribution correlated well with myelin density in different brain regions. CONCLUSION: This study showed that PET imaging of demyelination and remyelination processes in focal lesions is feasible. Our comparison of three myelin tracers showed that [(11)C]MeDAS has more favourable properties for quantitative PET imaging of demyelinated and remyelinated lesions throughout the CNS than [(11)C]CIC and [(11)C]PIB.


Subject(s)
Aniline Compounds/pharmacokinetics , Benzothiazoles/pharmacokinetics , Encephalomyelitis, Autoimmune, Experimental/diagnostic imaging , Multiple Sclerosis/diagnostic imaging , Myelin Sheath/diagnostic imaging , Radiopharmaceuticals/pharmacokinetics , Stilbenes/pharmacokinetics , Animals , Male , Radionuclide Imaging , Rats , Rats, Sprague-Dawley , Thiazoles
13.
Radiol. bras ; 44(1): 47-51, jan.-fev. 2011. ilus, tab
Article in Portuguese | LILACS | ID: lil-579006

ABSTRACT

OBJETIVO: Estabelecer os custos dos controles de qualidade para os radiofármacos marcados com [99mTc]tecnécio nos serviços de medicina nuclear do Brasil, em atenção às resoluções RDC nº 38/2008 e RDC nº 63/2009 editadas pela Agência Nacional de Vigilância Sanitária. MATERIAIS E MÉTODOS: Foram apurados preços de materiais de consumo, equipamentos e de mão-de-obra para a realização dos controles de qualidade. Os valores foram convertidos para unidades de volume, tempo e outras unidades cabíveis para a determinação do preço unitário. RESULTADOS: O investimento para aquisição de materiais de consumo e equipamentos foi estimado ser de R$ 35.500,00. O custo final para o controle de cada kit variou entre R$ 6,44 e R$ 7,80, dependendo do produto a ser analisado e do profissional selecionado para execução do procedimento. Esses valores podem representar de 0,5 por cento a 10 por cento do valor recebido pelas instituições pela realização dos exames. Na prática, o custo efetivo pode ser menor, uma vez que o produto de um kit pode ser utilizado em diversos pacientes. CONCLUSÃO: Em face do ganho de qualidade e segurança dos pacientes, concluímos que os custos da implantação do programa de controle de qualidade podem ser absorvidos no planejamento financeiro dos serviços de medicina nuclear.


OBJECTIVE: To establish the costs for quality control of [99mTc]technetium radiopharmaceuticals in Brazilian nuclear medicine centers, in compliance with Agência Nacional de Vigilância Sanitária (National Health Surveillance Agency) resolutions RDC No. 38/2008 and No. 63/2009. MATERIALS AND METHODS: Prices for consumables, equipment and labor involved in quality control procedures were calculated and the values were converted into units of volume, time or other appropriate units for use in mathematical formulas for determining unit prices. RESULTS: Estimated investment for acquisition of consumables and equipment was R$ 35,500.00. The final unit cost for quality control of a [99mTc]technetium radiopharmaceutical kit ranged from R$ 6.44 to R$ 7.80 per kit, depending on the product under analysis, on the methodology applied and on the qualification of the professional involved in the process. Such values may correspond to 0.5 percent to 10 percent of the amount received by the institution per diagnostic procedure. In practice the effective cost might be lower, considering that a single labeled kit can be fractionated into several doses. CONCLUSION: Considering the gains in quality and patients' safety, the authors conclude that costs for implementing a quality control program for radiopharmaceuticals can be absorbed in the financial planning of nuclear medicine centers.


Subject(s)
Humans , Male , Female , Adult , Radiopharmaceuticals/economics , Nuclear Medicine , Radiopharmaceuticals , Technetium/economics , Brazil , Brazilian Health Surveillance Agency , Cost-Benefit Analysis , Quality Control
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