Quantitative 1H MRI, 19F MRI, and 19F MRS of cell-internalized perfluorocarbon paramagnetic nanoparticles

M.B. Kok, A. de Vries, D. Abdurrachim, J.J. Prompers, H. Grull, K. Nicolay, G.J. Strijkers (Corresponding author)

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    Abstract

    In vivo molecular imaging with targeted MRI contrast agents will require sensitive methods to quantify local concentrations of contrast agent, enabling not only imaging-based recognition of pathological biomarkers but also detection of changes in expression levels as a consequence of disease development, therapeutic interventions or recurrence of disease. In recent years, targeted paramagnetic perfluorocarbon emulsions have been frequently applied in this context, permitting high-resolution 1H MRI combined with quantitative 19F MR imaging or spectroscopy, under the assumption that the fluorine signal is not altered by the local tissue and cellular environment. In this in vitro study we have investigated the 19F MR-based quantification potential of a paramagnetic perfluorocarbon emulsion conjugated with RGD-peptide to target the cell-internalizing a¿ß3-integrin expressed on endothelial cells, using a combination of 1H MRI, 19F MRI and 19F MRS. The cells took up the targeted emulsion to a greater extent than nontargeted emulsion. The targeted emulsion was internalized into large 1-7µm diameter vesicles in the perinuclear region, whereas nontargeted emulsion ended up in 1-4µm diameter vesicles, which were more evenly distributed in the cytoplasm. Association of the targeted emulsion with the cells resulted in different proton longitudinal relaxivity values, r1, for targeted and control nanoparticles, prohibiting unambiguous quantification of local contrast agent concentration. Upon cellular association, the fluorine R1 was constant with concentration, while the fluorine R2 increased nonlinearly with concentration. Even though the fluorine relaxation rate was not constant, the 19F MRI and 19F MRS signals for both targeted nanoparticles and controls were linear and quantifiable as function of nanoparticle concentration. © 2010 John Wiley & Sons, Ltd.
    Original languageEnglish
    Pages (from-to)19-27
    Number of pages9
    JournalContrast Media and Molecular Imaging
    Volume6
    Issue number1
    DOIs
    Publication statusPublished - 2011

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