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Perfluorocarbon lipid nanoparticles for dual-frequency MR Neuroimaging applications

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Gambino,  G
Research Group MR Neuroimaging Agents, Max Planck Institute for Biological Cybernetics, Max Planck Society;
Max Planck Institute for Biological Cybernetics, Max Planck Society;

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Savić,  T
Research Group MR Neuroimaging Agents, Max Planck Institute for Biological Cybernetics, Max Planck Society;
Max Planck Institute for Biological Cybernetics, Max Planck Society;

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Angelovski,  G
Research Group MR Neuroimaging Agents, Max Planck Institute for Biological Cybernetics, Max Planck Society;
Max Planck Institute for Biological Cybernetics, Max Planck Society;

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Citation

Gambino, G., Savić, T., & Angelovski, G. (2019). Perfluorocarbon lipid nanoparticles for dual-frequency MR Neuroimaging applications. In 14th Annual Meeting of the European Society for Molecular Imaging (EMIM 2019).


Cite as: http://hdl.handle.net/21.11116/0000-0003-0F79-6
Abstract
Introduction Although BOLD-based fMRI is extensively used to indicate neuronal activity, a great step forward in detecting brain activity directly would be the measurement of [Ca2+] by means of bioresponsive MRI contrast agents, probes able to modulate their signal-enhancement effect in response to [Ca2+] fluctuations. Here we report a lipid nanoparticle (GdPFLNPs) with a surface bearing Ca-responsive Gd3+ complexes (GdL) and a perfluorocarbon core. Such nanoprobe would enable the dual-frequency imaging of [Ca2+], coregistering its 1H MRI Ca-enhanced contrast with the quantitative signal of 19F MRI. Methods The lipid nanoparticles were obtained through the rehydration of a lipid film (L/DPPC/DSPE-PEG2000 in 20:75:5 ratio) with a suspension of perfluoro-15-crown-5-ether (PFCE) in aqueous HEPES and NaCl. The obtained suspension was sonicated and extruded with 200 nm cutoff filters. Complexation was performed after extrusion in order to decorate with Gd3+ exclusively the ligand molecules exposed on the outer nanoparticle surface. The final nanoparticles were purified by dialysis and ultracentrifugation. The size and shape of the obtained particles were assessed by dynamic light scattering (DLS) and cryo-TEM imaging, the relaxometric properties were characterized by 1H and 19F NMR spectrometry, while the imaging potential was demonstrated by means of 1H and 19F MRI on tube phantoms at 7 T. Results/Discussion The obtained suspension was analyzed by DLS resulting in a polydisperse system, with particle diameter of 78.2 nm and 236.9 nm (PDI 0.30). Cryo-TEM images confirmed the size distribution of the sample and revealed particles of spherical shape with an electron-dense core, characteristic for this kind of system.1 Furthermore, no evident change of size or shape of the particles seems to occur upon binding of Ca2+. The potential of GdPFLPNs as Ca-responsive 1H MRI contrast agents was characterized by means of relaxometric titrations at 25 °C and 7 T (Figure 1), resulting in a significant increase of longitudinal and transverse relaxivities, r1 (+31%) and r2 (+343%), respectively. On the other hand, 19F T1 value (974 ms) did not change throughout the titration. Additionally, 1H MRI on tube phantoms showed the great potential of this system as T2w and T2/T1w Ca-responsive agent, while 19F T1w MRI images of the samples exhibited very high SNR for corresponding low [Gd3+] samples (Figure 2). Conclusions In this work we report a nanosized Ca-responsive probe for dual-frequency MRI. The possibility of exploiting its advantageous performances as T2- and T2/T1-sensitive contrast agent, together with the high SNR obtained with quantitative 19F MRI, opens new realms for a wide range of possible future applications, focused on the monitoring and mapping of [Ca2+] in the brain, such as Ca-dependent molecular- and stimuli-coupled functional neuroimaging.