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Cunha L.,Polytechnic Institute of Porto | Szigeti K.,Semmelweis University | Mathe D.,CROmed Ltd. | Metello L.F.,Polytechnic Institute of Porto | Metello L.F.,IsoPor SA
Drug Discovery Today | Year: 2014

Drug development represents a highly complex, inefficient and costly process. Over the past decade, the widespread use of nuclear imaging, owing to its functional and molecular nature, has proven to be a determinant in improving the efficiency in selecting the candidate drugs that should either be abandoned or moved forward into clinical trials. This helps not only with the development of safer and effective drugs but also with the shortening of time-to-market. The modern concept and future trends concerning molecular imaging will assumedly be hybrid or multimodality imaging, including combinations between high sensitivity and functional (molecular) modalities with high spatial resolution and morphological techniques. © 2014 Elsevier Ltd.

Cui X.,Kings College London | Belo S.,Kings College London | Kruger D.,Kings College London | Yan Y.,University of Nottingham | And 12 more authors.
Biomaterials | Year: 2014

Magnetic nanoparticles (NPs) MnFe2O4 and Fe3O4 were stabilised by depositing an Al(OH)3 layer via a hydrolysis process. The particles displayed excellent colloidal stability in water and a high affinity to [18F]-fluoride and bisphosphonate groups. A high radiolabeling efficiency, 97% for 18F-fluoride and 100% for 64Cu-bisphosphonate conjugate, was achieved by simply incubating NPs with radioactivity solution at room temperature for 5min. The properties of particles were strongly dependant on the thickness and hardness of the Al(OH)3 layer which could in turn be controlled by the hydrolysis method. The application of these Al(OH)3 coated magnetic NPs in molecular imaging has been further explored. The results demonstrated that these NPs are potential candidates as dual modal probes for MR and PET. Invivo PET imaging showed a slow release of 18F from NPs, but no sign of efflux of 64Cu. © 2014 The Authors.

Cunha L.,Polytechnic Institute of Porto | Cunha L.,University of Porto | Horvath I.,Semmelweis University | Ferreira S.,Polytechnic Institute of Porto | And 9 more authors.
Molecular Diagnosis and Therapy | Year: 2014

Translational research is changing the practice of modern medicine and the way in which health problems are approached and solved. The use of small-animal models in basic and preclinical sciences is a major keystone for these kinds of research and development strategies, representing a bridge between discoveries at the molecular level and clinical implementation in diagnostics and/or therapeutics. The development of high-resolution in vivo imaging technologies provides a unique opportunity for studying disease in real time, in a quantitative way, at the molecular level, along with the ability to repeatedly and non-invasively monitor disease progression or response to treatment. The greatest advantages of preclinical imaging techniques include the reduction of biological variability and the opportunity to acquire, in continuity, an impressive amount of unique information (without interfering with the biological process under study) in distinct forms, repeated or modulated as needed, along with the substantial reduction in the number of animals required for a particular study, fully complying with 3R (Replacement, Reduction and Refinement) policies. The most suitable modalities for small-animal in vivo imaging applications are based on nuclear medicine techniques (essentially, positron emission tomography [PET] and single photon emission computed tomography [SPECT]), optical imaging (OI), computed tomography (CT), magnetic resonance imaging (MRI), magnetic resonance spectroscopy imaging (MRSI), and ultrasound. Each modality has intrinsic advantages and limitations. More recently, aiming to overcome the inherent limitations of each imaging modality, multimodality devices designed to provide complementary information upon the pathophysiological process under study have gained popularity. The combination of high-resolution modalities, like micro-CT or micro-MRI, with highly sensitive techniques providing functional information, such as micro-PET or micro-SPECT, will continue to broaden the horizons of research in such key areas as infection, oncology, cardiology, and neurology, contributing not only to the understanding of the underlying mechanisms of disease, but also providing efficient and unique tools for evaluating new chemical entities and candidate drugs. The added value of small-animal imaging techniques has driven their increasing use by pharmaceutical companies, contract research organizations, and research institutions. © 2013 Springer International Publishing.

Cui X.,Kings College London | Green M.A.,Kings College London | Blower P.J.,Kings College London | Zhou D.,Loughborough University | And 6 more authors.
Chemical Communications | Year: 2015

Magnetic and fluorescent hydroxyapatite nanoparticles were synthesised using Al(OH)3-stabilised MnFe2O4 or Fe3O4 nanoparticles as precursors. They were readily and efficiently radiolabelled with 18F. Bisphosphonate polyethylene glycol polymers were utilised to endow the nanoparticles with excellent colloidal stability in water and to incorporate cyclam for high affinity labelling with 64Cu. This journal is © The Royal Society of Chemistry 2015.

Botz B.,University of Pecs | Bolcskei K.,University of Pecs | Kereskai L.,University of Pecs | Kovacs M.,Semmelweis University | And 11 more authors.
Arthritis and Rheumatology | Year: 2014

Objective Pituitary adenylate cyclase-activating polypeptide (PACAP) expressed in capsaicin-sensitive sensory neurons and immune cells has divergent functions in inflammatory and pain processes. This study was undertaken to investigate the involvement of PACAP in a mouse model of rheumatoid arthritis.Methods Arthritis was induced in PACAP-/- and wild-type (PACAP+/+) mice by K/BxN serum transfer. General features of the disease were investigated by semiquantitative scoring, plethysmometry, and histopathologic analysis. Mechano- and thermonociceptive thresholds and motor functions were also evaluated. Metabolic activity was assessed by positron emission tomography. Bone morphology was measured by in vivo micro-computed tomography, myeloperoxidase activity and superoxide production by bioluminescence imaging with luminol and lucigenin, respectively, and vascular permeability by fluorescent indocyanine green dye study.Results PACAP+/+ mice developed notable joint swelling, reduced grasping ability, and mechanical (but not thermal) hyperalgesia after K/BxN serum transfer. In PACAP-/- mice clinical scores and edema were significantly reduced, and mechanical hyperalgesia and motor impairment were absent, throughout the 2-week period of observation. Metabolic activity and superoxide production increased in the tibiotarsal joints of wild-type mice but were significantly lower in PACAP-/- animals. Myeloperoxidase activity in the ankle joints of PACAP-/- mice was significantly reduced in the early phase of arthritis, but increased in the late phase. Synovial hyperplasia was also significantly increased, and progressive bone spur formation was observed in PACAP-deficient mice only.Conclusion In PACAP-deficient mice with serum-transfer arthritis, joint swelling, vascular leakage, hyperalgesia, and early inflammatory cell accumulation are reduced; in the later phase of the disease, immune cell function and bone neoformation are increased. Elucidation of the underlying pathways of PACAP activity may open promising new avenues for development of therapy in inflammatory arthritis. © 2014 The Authors. Arthritis & Rheumatology is published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology. Copyright © 2014 by the American College of Rheumatology.

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