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1.
Bioconjug Chem ; 27(2): 319-28, 2016 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-26172432

RESUMO

Multimodal nanoparticulate materials are described, offering magnetic, radionuclide, and fluorescent imaging capabilities to exploit the complementary advantages of magnetic resonance imaging (MRI), positron emission tomography/single-photon emission commuted tomography (PET/SPECT), and optical imaging. They comprise Fe3O4@NaYF4 core/shell nanoparticles (NPs) with different cation dopants in the shell or core, including Co0.16Fe2.84O4@NaYF4(Yb, Er) and Fe3O4@NaYF4(Yb, Tm). These NPs are stabilized by bisphosphonate polyethylene glycol conjugates (BP-PEG), and then show a high transverse relaxivity (r2) up to 326 mM(-1) s(-1) at 3T, a high affinity to [(18)F]-fluoride or radiometal-bisphosphonate conjugates (e.g., (64)Cu and (99m)Tc), and fluorescent emissions from 500 to 800 nm under excitation at 980 nm. The biodistribution of intravenously administered particles determined by PET/MR imaging suggests that negatively charged Co0.16Fe2.84O4@NaYF4(Yb, Er)-BP-PEG (10K) NPs cleared from the blood pool more slowly than positively charged NPs Fe3O4@NaYF4(Yb, Tm)-BP-PEG (2K). Preliminary results in sentinel lymph node imaging in mice indicate the advantages of multimodal imaging.


Assuntos
Óxido Ferroso-Férrico/química , Fluoretos/química , Imageamento por Ressonância Magnética/métodos , Nanopartículas/química , Imagem Óptica/métodos , Tomografia por Emissão de Pósitrons/métodos , Ítrio/química , Animais , Difosfonatos/química , Difosfonatos/farmacocinética , Óxido Ferroso-Férrico/farmacocinética , Fluoretos/farmacocinética , Masculino , Camundongos Endogâmicos C57BL , Camundongos Nus , Imagem Multimodal/métodos , Polietilenoglicóis/química , Polietilenoglicóis/farmacocinética , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Ítrio/farmacocinética
2.
J Cereb Blood Flow Metab ; 35(12): 1921-9, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26219594

RESUMO

Inflammation that develops in the brain and peripheral organs after stroke contributes profoundly to poor outcome of patients. However, mechanisms through which inflammation impacts on brain injury and overall outcome are improperly understood, in part because the earliest inflammatory events after brain injury are not revealed by current imaging tools. Here, we show that single-photon emission computed tomography (NanoSPECT/CT Plus) allows visualization of blood brain barrier (BBB) injury after experimental stroke well before changes can be detected with magnetic resonance imaging (MRI). Early 99mTc-DTPA (diethylene triamine pentaacetic acid) signal changes predict infarct development and systemic inflammation preceding experimental stroke leads to very early perfusion deficits and increased BBB injury within 2 hours after the onset of ischemia. Acute brain injury also leads to peripheral inflammation and immunosuppression, which contribute to poor outcome of stroke patients. The SPECT imaging revealed early (within 2 hours) changes in perfusion, barrier function and inflammation in the lungs and the gut after experimental stroke, with good predictive value for the development of histopathologic changes at later time points. Collectively, visualization of early inflammatory changes after stroke could open new translational research avenues to elucidate the interactions between central and peripheral inflammation and to evaluate in vivo 'multi-system' effects of putative anti-inflammatory treatments.


Assuntos
Isquemia Encefálica/diagnóstico por imagem , Inflamação/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Animais , Barreira Hematoencefálica/diagnóstico por imagem , Barreira Hematoencefálica/patologia , Isquemia Encefálica/patologia , Trato Gastrointestinal/patologia , Processamento de Imagem Assistida por Computador , Terapia de Imunossupressão , Infarto da Artéria Cerebral Média/diagnóstico por imagem , Infarto da Artéria Cerebral Média/patologia , Inflamação/patologia , Pulmão/patologia , Imageamento por Ressonância Magnética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Doenças do Sistema Nervoso/etiologia , Doenças do Sistema Nervoso/psicologia , Compostos Radiofarmacêuticos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/patologia , Pentetato de Tecnécio Tc 99m
3.
Biomaterials ; 35(22): 5840-6, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24768194

RESUMO

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 [(18)F]-fluoride and bisphosphonate groups. A high radiolabeling efficiency, 97% for (18)F-fluoride and 100% for (64)Cu-bisphosphonate conjugate, was achieved by simply incubating NPs with radioactivity solution at room temperature for 5 min. 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. In vivo PET imaging showed a slow release of (18)F from NPs, but no sign of efflux of (64)Cu.


Assuntos
Hidróxido de Alumínio , Meios de Contraste , Compostos Férricos , Óxido Ferroso-Férrico , Compostos de Manganês , Nanopartículas , Hidróxido de Alumínio/química , Animais , Meios de Contraste/química , Feminino , Compostos Férricos/química , Óxido Ferroso-Férrico/química , Radioisótopos de Flúor/química , Imageamento por Ressonância Magnética , Compostos de Manganês/química , Camundongos , Nanopartículas/química , Tomografia por Emissão de Pósitrons
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