Institute DAlta Tecnologia

Barcelona, Spain

Institute DAlta Tecnologia

Barcelona, Spain
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Rojas S.,Institute dAlta Tecnologia | Martin A.,CIC Biomagune | Pareto D.,Institute dAlta Tecnologia | Herance J.R.,Institute dAlta Tecnologia | And 7 more authors.
Neuroscience | Year: 2011

Background and purpose: Positron emission tomography (PET) studies in humans have used 11C-flumazenil (FMZ) to assess neuronal viability after stroke. Here we aimed to study whether 11C-FMZ binding was sensitive to neuronal damage in the acute phase following ischemia/reperfusion in the rat brain. Experimental procedures: Transient (2 h followed by reperfusion) and permanent intraluminal middle cerebral artery occlusion was carried out. 11C-FMZ binding was studied by PET up to 24 h after the onset of ischemia. Tissue infarction was evaluated post-mortem at 24 h. Immunohistochemistry against a neuronal nuclei specific protein (NeuN) was performed to assess neuronal injury. Results: No decrease in 11C-FMZ binding was detected in the ipsilateral cortex up to 24 h post-ischemia in the model of transient occlusion despite the fact that rats developed cortical and striatal infarction, and neuronal injury was clearly apparent at this time. In contrast, 11C-FMZ binding was significantly depressed in the ipsilateral cortex at 24 h following permanent ischemia. Conclusions: This finding evidences that 11C-FMZ binding is not sensitive to neuronal damage on the acute phase of ischemia/reperfusion in the rat brain. © 2011 IBRO.


Radua J.,King's College London | Radua J.,Institute dAlta Tecnologia | Phillips M.L.,University of Pittsburgh | Phillips M.L.,University of Cardiff | And 10 more authors.
NeuroImage | Year: 2010

Perception of fearful faces is associated with functional activation of cortico-limbic structures, which has been found altered in individuals with psychiatric disorders such as schizophrenia, autism and major depression. The objective of this study was to isolate the brain response to the features of standardized fearful faces by incorporating principal component analysis (PCA) into the analysis of neuroimaging data of healthy volunteers and individuals with schizophrenia. At the first stage, the visual characteristics of morphed fearful facial expressions (FEEST, Young et al., 2002) were classified with PCA, which produced seven orthogonal factors, with some of them related to emotionally salient facial features (eyes, mouth, brows) and others reflecting non-salient facial features. Subsequently, these PCA-based factors were included into the functional magnetic resonance imaging (fMRI) analysis of 63 healthy volunteers and 32 individuals with schizophrenia performing a task that involved implicit processing of FEEST stimuli. In healthy volunteers, significant neural response was found to visual characteristics of eyes, mouth or brows. In individuals with schizophrenia, PCA-based analysis enabled us to identify several significant clusters of activation that were not detected by the standard approach. These clusters were implicated in processing of visual and emotional information and were attributable to the perception of eyes and brows. PCA-based analysis could be useful in isolating brain response to salient facial features in psychiatric populations. © 2009 Elsevier Inc. All rights reserved.


Gispert J.D.,Barcelonabeta Brain Research Center | Figueiras F.P.,Institute dAlta Tecnologia | Vengeliene V.,University of Heidelberg | Herance J.R.,Vall dHebron Research Institute VHIR | And 2 more authors.
Behavioural Brain Research | Year: 2017

Several [18F]-FDG positron emission tomography (PET) studies in alcoholics have consistently reported decreases in overall brain glucose metabolism at rest and following acute alcohol administration. However, changes in cerebral glucose utilization associated with the transition to addiction are not well understood and require longitudinal translational imaging studies in animal models of alcoholism. Here, we studied brain glucose uptake in alcohol drinking rats in order to provide convergent evidence to what has previously been reported in human studies. Brain glucose metabolism was measured by [18F]-FDG microPET imaging in different male Wistar rat groups: short-term drinking (three months), long-term drinking (twelve months) and alcohol-naïve. Global and regional cerebral glucose uptake was measured at rest and following acute alcohol administration. We showed that alcohol significantly reduced the whole-brain glucose metabolism. This effect was most pronounced in the parietal cortex and cerebellum. Alcohol-induced decreases in brain [18F]-FDG uptake was most apparent in alcohol-naïve rats, less intense in short-term drinkers and absent in long-term drinkers. The latter finding indicates the occurrence of tolerance to the intoxicating effects of alcohol in long-term drinking individuals. In contrast, some regions, like the ventral striatum and entorhinal cortex, showed enhanced metabolic activity, an effect that did not undergo tolerance during long-term alcohol consumption. Our findings are comparable to those described in human studies using the same methodology. We conclude that [18F]-FDG PET studies in rat models of alcoholism provide good translation and can be used for future longitudinal studies investigating alterations in brain function during different stages of the addiction cycle. © 2017 Elsevier B.V.


Rojas S.,Center dImatge Molecular | Herance J.R.,Center dImatge Molecular | Gispert J.D.,Institute dAlta Tecnologia | Abad S.,Center dImatge Molecular | And 8 more authors.
Neurobiology of Aging | Year: 2013

Positron emission tomography (PET) has been used extensively to evaluate the neuropathology of Alzheimer's disease (AD) in vivo. Radiotracers directed toward the amyloid deposition such as [18F]-FDDNP (2-(1-{6-[(2-[F]Fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile) and [11C]-PIB (Pittsburg compound B) have shown exceptional value in animal models and AD patients. Previously, the glucose analogue [18F]-FDG (2-[(18)F]fluorodeoxyglucose) allowed researchers and clinicians to evaluate the brain glucose consumption and proved its utility for the early diagnosis and the monitoring of the progression of AD. Animal models of AD are based on the transgenic expression of different human mutant genes linked to familial AD. The novel transgenic 5XFAD mouse containing 5 mutated genes in its genome has been proposed as an AD model with rapid and massive cerebral amyloid deposition. PET studies performed with animal-dedicated scanners indicate that PET with amyloid-targeted radiotracers can detect the pathological amyloid deposition in transgenic mice and rats. However, in other studies no differences were found between transgenic mice and their wild type littermates. We sought to investigate in 5XFAD mice if the radiotracers [11C]-PIB, and [18F]-Florbetapir could quantify the amyloid deposition in vivo and if [18F]-FDG could do so with regard to glucose consumption. We found that 5XFAD animals presented higher cerebral binding of [18F]-Florbetapir, [11C]-PIB, and [18F]-FDG. These results support the use of amyloid PET radiotracers for the evaluation of AD animal models. Probably, the increased uptake observed with [18F]-FDG is a consequence of glial activation that occurs in 5XFAD mice. © 2013 Elsevier Inc.


Abate-Daga D.,Institute DInvestigacions Biomediques August Pi i Sunyer IDIBAPS | Andreu N.,Research Center Biomedica En Red Of Enfermedades Raras Ciberer | Camacho-Sanchez J.,Lhospitalet Of Llobregat | Alemany R.,Lhospitalet Of Llobregat | And 4 more authors.
PLoS ONE | Year: 2011

Replication-competent adenoviruses armed with thymidine kinase (TK) combine the concepts of virotherapy and suicide gene therapy. Moreover TK-activity can be detected by noninvasive positron emission-computed tomography (PET) imaging, what could potentially facilitate virus monitoring in vivo. Here, we report the generation of a novel oncolytic adenovirus that incorporates the Tat8-TK gene under the control of the Major Late Promoter in a highly selective backbone thus providing selectivity by targeting the retinoblastoma pathway. The selective oncolytic TK virus, termed ICOVIR5-TK-L, showed reduced potency compared to a non-selective counterpart. However the combination of ICOVIR5-TK-L with ganciclovir (GCV) induced a potent antitumoural effect similar to that of wild type adenovirus in a preclinical model of pancreatic cancer. Although the treatment with GCV provoked a reduction in the viral yield, both in vitro and in vivo, a two-cycle treatment of virus and GCV resulted in an enhanced antitumoral response that correlated with high TK-activity, based on microPET measurements. Thus, TK-expressing oncolytic adenoviruses can be traced by PET imaging providing real time information on the activity of the virus and its antitumoral potency can be optimized by GCV dosing. © 2011 Abate-Daga et al.


Gironell A.,Autonomous University of Barcelona | Figueiras F.P.,Institute dAlta Tecnologia | Pagonabarraga J.,Autonomous University of Barcelona | Herance J.R.,Institute dAlta Tecnologia | And 2 more authors.
Parkinsonism and Related Disorders | Year: 2012

Background: Essential tremor is the most common movement disorder in adults, but its exact etiology and pathophysiology are still not fully understood. There is some consensus, however, about the involvement of the cerebellum and accumulating evidence points towards a dysfunction of the gabaergic system. We hypothesize that the serotonin neurotransmission system may also play a role as it does in tremor in Parkinson disease. This study aimed to investigate the association between the severity of tremor symptoms and the gabaergic and serotoninergic neurotransmission systems in essential tremor. Material and methods: We measured the tremor clinical rating scale score and acquired DASB and Flumazenil PET scans in 10 patients who presented with essential tremor at different stages of clinical severity. Statistically significant correlations were sought between the scale scores and parametric binding potential images. Results: The correlation analysis of cerebellar Flumazenil uptake and tremor clinical rating scale scores reached statistical significance (R2 = 0.423, p = 0.041), whereas no association was detected in the DASB scans. Conclusions: The severity of tremor correlated with the abnormalities found in GABA receptor binding, suggesting a primary gabaergic deficiency or a functional abnormality at the level of GABAA receptor subtypes. These results may assist in the rational development of new pharmacological treatments for essential tremor. © 2012 Elsevier Ltd.


Rojas S.,Center matge Molecular CIM | Gispert J.D.,Institute DAlta Tecnologia | Abad S.,Center matge Molecular CIM | Buaki-Sogo M.,Polytechnic University of Valencia | And 4 more authors.
Molecular Pharmaceutics | Year: 2012

A variety of nanoparticles have been proposed for several biomedical applications. To gauge the therapeutic potential of these nanoparticles, in vivo biodistribution is essential and mandatory. In the present study, ceria nanoparticles (5 nm average particle size) were labeled with 18F to study their in vivo biodistribution in rats by positron emission tomography (PET). The 18F isotope was anchored by reaction of N-succinimidyl 4-[18F]fluorobenzoate (18F-SFB) with a modified nanoparticle surface obtained by silylation with 3-aminopropylsilyl. Radiolabeled ceria nanoparticles accumulated mainly in lungs, spleen, and liver. Metabolic products of the radiolabeled nanoparticulate material were excreted into the urinary tract. © 2012 American Chemical Society.


Guerrero S.,University of Chile | Herance J.R.,Institute dAlta Tecnologia | Rojas S.,Institute dAlta Tecnologia | Mena J.F.,University of Chile | And 8 more authors.
Bioconjugate Chemistry | Year: 2012

Gold nanoparticles (AuNPs) have been extensively used in biological applications because of their biocompatibility, size, and ease of characterization, as well as an extensive knowledge of their surface chemistry. These features make AuNPs readily exploitable for biomedical applications, including drug delivery and novel diagnostic and therapeutic approaches. In a previous work, we studied ex vivo distribution of the conjugate C(AuNP)-LPFFD for its potential uses in the treatment of Alzheimer's disease. In this study, we covalently labeled the conjugate with [ 18F]-fluorobenzoate to study the in vivo distribution of the AuNP by positron emission tomography (PET). After intravenous administration in rat, the highest concentration of the radiolabeled conjugate was found in the bladder and urine with a lower proportion in the intestine, demonstrating progressive accumulation compatible with biliary excretion of the conjugate. The conjugate also accumulated in the liver and spleen. PET imaging allowed us to study the in vivo biodistribution of the AuNPs in a noninvasive and sensitive way using a reduced number of animals. Our results show that AuNPs can be covalently and radioactively labeled for PET biodistribution studies. © 2012 American Chemical Society.


Martin R.,Polytechnic University of Valencia | Menchon C.,Institute DAlta Tecnologia | Apostolova N.,University of Valencia | Victor V.M.,University of Valencia | And 3 more authors.
ACS Nano | Year: 2010

Diamond nanoparticles (DNPs) obtained by explosive detonation have become commercially available. These commercial DNPs can be treated under Fenton conditions (FeSO4 and H2O2 at acidic pH) to obtain purer DNP samples with a small average particle size (4 nm) and a large population of surface OH groups (HO-DNPs). These Fenton-treated HO-DNPs have been used as a support of gold and platinum nanoparticles (≤2 nm average size). The resulting materials (Au/HO-DNP and Pt/HO-DNP) exhibit a high antioxidant activity against reactive oxygen species induced in a hepatoma cell line. In addition to presenting good biocompatibility, Au/HO- and Pt/HO-DNP exhibit about a two-fold higher antioxidant activity than glutathione, one of the reference antioxidant systems. The most active material against cellular oxidative stress was Au/HO-DNP. © 2010 American Chemical Society.


Romero A.,Autonomous University of Barcelona | Rojas S.,Institute dAlta Tecnologia | Cabanero D.,Autonomous University of Barcelona | Gispert J.D.,Institute dAlta Tecnologia | And 3 more authors.
Anesthesiology | Year: 2011

Background: Neuroplastic changes involved in latent pain sensitization after surgery are poorly defined. We assessed temporal changes in glucose brain metabolism in a postoperative rat model using positron emission tomography. We also investigated brain metabolism after naloxone administration. Methods: Rats were given remifentanil anesthetic and underwent a plantar incision, with 1 mg/kg of (-)-naloxone subcutaneously administered on postoperative days 20 and 21. Using the von Frey test, mechanical thresholds were measured pre-and postoperatively at different time points in awake animals during F-fluorodeoxyglucose (F-FDG) uptake. Brain images were also obtained the day before mechanical testing, using a positron emission tomography R4 scanner (Concorde Microsystems, Siemens, Knoxville, TN). Differences in brain activity were assessed utilizing a statistical parametric mapping. RESULTS:: Surgery induced minor changes in F-FDG uptake in the cerebellum, hippocampus, and posterior cortex, which extended to the thalamus, hypothalamus, and brainstem on days 6 and 7. Changes were still present on day 21. Maximal postoperative hypersensitivity was observed on day 2. The administration of (-)-naloxone on day 21 induced significant hypersensitivity, greatly enhancing the effect on F-FDG uptake. In sham-operated rats, naloxone induced changes limited to the striatum and the cerebellum. Nonnociceptive stimulation with von Frey filaments had no effect on F-FDG uptake. Conclusions: Surgery, remifentanil, and their combination induced long-lasting and significant metabolic changes in the pain brain matrix, with a positive correlation with hypersensitivity after naloxone. Changes in brain F-FDG precipitated by naloxone suggest that surgery under remifentanil anesthetic induces the greatest neuroplastic brain adaptations in opioid-related pathways involved in nociceptive processing and long-lasting pain sensitization. © 2011 the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins. Anesthesiology.

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