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Incorporation of paramagnetic, fluorescent and PET/SPECT contrast agents into liposomes for multimodal imaging.

Mitchell, N; Kalber, TL; Cooper, MS; Sunassee, K; Chalker, SL; Shaw, KP; Ordidge, KL; ... Tabor, AB; + view all (2013) Incorporation of paramagnetic, fluorescent and PET/SPECT contrast agents into liposomes for multimodal imaging. Biomaterials , 34 (4) 1179 - 1192. 10.1016/j.biomaterials.2012.09.070. Green open access

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Abstract

A series of metal-chelating lipid conjugates has been designed and synthesized. Each member of the series bears a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) macrocycle attached to the lipid head group, using short n-ethylene glycol (n-EG) spacers of varying length. Liposomes incorporating these lipids, chelated to Gd(3+), (64)Cu(2+), or (111)In(3+), and also incorporating fluorescent lipids, have been prepared, and their application in optical, magnetic resonance (MR) and single-photon emission tomography (SPECT) imaging of cellular uptake and distribution investigated in vitro and in vivo. We have shown that these multimodal liposomes can be used as functional MR contrast agents as well as radionuclide tracers for SPECT, and that they can be optimized for each application. When shielded liposomes were formulated incorporating 50% of a lipid with a short n-EG spacer, to give nanoparticles with a shallow but even coverage of n-EG, they showed good cellular internalization in a range of tumour cells, compared to the limited cellular uptake of conventional shielded liposomes formulated with 7% 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[carboxy(polyethyleneglycol)(2000)] (DSPE-PEG2000). Moreover, by matching the depth of n-EG coverage to the length of the n-EG spacers of the DOTA lipids, we have shown that similar distributions and blood half lives to DSPE-PEG2000-stabilized liposomes can be achieved. The ability to tune the imaging properties and distribution of these liposomes allows for the future development of a flexible tri-modal imaging agent.

Type: Article
Title: Incorporation of paramagnetic, fluorescent and PET/SPECT contrast agents into liposomes for multimodal imaging.
Location: Netherlands
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.biomaterials.2012.09.070
Publisher version: http://dx.doi.org/10.1016/j.biomaterials.2012.09.0...
Language: English
Additional information: This work is made available under a Creative Commons license. PMCID: PMC3520009
Keywords: Contrast Media, Liposomes, Magnetic Resonance Imaging, Microscopy, Fluorescence, Nanocapsules, Subtraction Technique, Tomography, Emission-Computed, Single-Photon
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Department of Imaging
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Experimental and Translational Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Respiratory Medicine
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Chemistry
URI: https://discovery.ucl.ac.uk/id/eprint/1372203
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