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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. Source

Ninerola-Baizan A.,CIBER ISCIII | Ninerola-Baizan A.,University of Barcelona | Rojas S.,Institute DAlta Tecnologia | Roe-Vellve N.,University of Barcelona | And 9 more authors.
Nuclear Medicine and Biology | Year: 2015

Introduction: Rodent models are extensively used to assess the biochemical and physiological changes associated with aging. They play a major role in the development of therapies for age-related pathologies such as Parkinson's disease. To validate the usefulness of these animal models in aging or age-related disease research, the consistency of cerebral aging processes across species must be evaluated. The dopaminergic system seems particularly susceptible to the aging process. One of the results of this susceptibility is a decline in striatal dopamine transporter (DAT) availability. Methods: We sought to ascertain whether similar age changes could be detected in-vivo in rats, using molecular imaging techniques such as single photon emission computed tomography (SPECT) with [123I]FP-CIT. Results: A significant decrease of 17.21% in the striatal specific uptake ratio was observed in the aged rats with respect to the young control group. Conclusions: Our findings suggest that age-related degeneration in the nigrostriatal track is similar in humans and rats, which supports the use of this animal in models to evaluate the effect of aging on the dopaminergic system. Advances in Knowledge and Implications for patient Care: Our findings indicate that age-related degeneration in the nigrostriatal track is similar in humans and rats and that these changes can be monitored in vivo using small animal SPECT with [123I]FP-CIT, which could facilitate the translational research in rat models of age related disorders of dopaminergic system. © 2015 Elsevier Inc. Source

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. Source

Moreno-Torres A.,Center Diagnostic Pedralbes | Moreno-Torres A.,CIBER ISCIII | Rosset-Llobet J.,Institute Of Fisiologia I Medicina Of Lart | Pujol J.,Institute DAlta Tecnologia | And 3 more authors.
PLoS ONE | Year: 2010

Background: Although non-specific pain in the upper limb muscles of workers engaged in mild repetitive tasks is a common occupational health problem, much is unknown about the associated structural and biochemical changes. In this study, we compared the muscle energy metabolism of the extrinsic finger extensor musculature in instrumentalists suffering from work-related pain with that of healthy control instrumentalists using non-invasive phosphorus magnetic resonance spectroscopy (31P-MRS). We hypothesize that the affected muscles will show alterations related with an impaired energy metabolism. Methodology/Principal Findings:We studied 19 volunteer instrumentalists (11 subjects with work-related pain affecting the extrinsic finger extensor musculature and 8 healthy controls). We used 31P-MRS to find deviations from the expected metabolic response to exercise in phosphocreatine (PCr), inorganic phosphate (Pi), Pi/PCr ratio and intracellular pH kinetics. We observed a reduced finger extensor exercise tolerance in instrumentalists with myalgia, an intracellular pH compartmentation in the form of neutral and acid compartments, as detected by Pi peak splitting in 31P-MRS spectra, predominantly in myalgic muscles, and a strong association of this pattern with the condition. Conclusions/Significance: Work-related pain in the finger extrinsic extensor muscles is associated with intracellular pH compartmentation during exercise, non-invasively detectable by 31P-MRS and consistent with the simultaneous energy production by oxidative metabolism and glycolysis. We speculate that a deficit in energy production by oxidative pathways may exist in the affected muscles. Two possible explanations for this would be the partial and/or local reduction of blood supply and the reduction of the muscle oxidative capacity itself. © 2010 Moreno-Torres et al. Source

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. Source

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