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Title: Synthesis and characterization of functionalized magnetoliposomes for Magnetic Resonance Imaging and theranostics applications
Authors: Garcia Ribeiro, Rita Sofia
Kektar-Atre, Ashwini
Soenen, Stefaan
De Cuyper, Marcel
Himmelreich, Uwe
Issue Date: 25-Nov-2014
Conference: YBMRS 2014 edition:13th location:Spa date:24-25 November 2014
Article number: YBMRS 2014‐ORAL COMMUNICATIONS 27
Abstract: Magnetoliposomes (MLs), which were earlier developed in our lab, consist of nanosized, magnetisable iron oxide cores (magnetite, Fe3O4) which are individually enveloped by a bilayer of phospholipid molecules. In the past, it was already shown that these structures are biocompatible imaging agents, resulting in a highly efficient labeling of cells without evoking toxic effects and with a powerful imaging signal that remains stable over a long time period (1). A unique feature of MLs is that the coating can be easily modified, for instance by inserting fluorescent or radioactive labels and/or targeting molecules into the lipid bilayer. Thus, these highly sophisticated MLs offer exciting possibilities for multimodal molecular imaging and drug delivery. Till now, in-house synthetized MLs were functionalized and characterized by Transmission Electron Microscopy (TEM) and Dynamic Light Scattering (DLS). The results were satisfactory in both techniques, with TEM defining the size (30-35 nm) and DLS the hydrodynamic diameter (45 nm) of the MLs, and with the morphology of the phospholipidic bilayers very discernible in the TEM images. These MLs were further employed for cell labeling and longitudinal in vivo imaging of prelabeled INS-1E cells and Pancreatic Islets (PIs). To test the MR detectability of cells labeled under different conditions, agarose phantoms were prepared and MR imaging was performed. Phantoms were scanned using a 3D T2*-weighted gradient echo sequence with a Fast Low Angle Shot sequence (FLASH, TR = 200 ms, TE = 15 ms) resulting in an isotropic resolution of 234 µm3. First proof-of-principle experiments were also successfully conducted to transplant the prelabeled cells and PIs in the kidney capsule and portal vein of C57Bl6 adult mice. Animals were scanned on the day of the islet engraftment and until 14 days post islet transplantation. A respiration-gated FLASH sequence (TE= 2.3ms, TR= 202.56ms, six slices with a thickness of 1mm and an in-plane resolution of 136µm2) was used to determine the decrease in the signal intensity due to labeled islets at the site of transplantation. All MR measurements were performed using a 9.4 T Bruker Biospec small animal MR scanner (Bruker Biospin, Ettlingen, Germany). The results obtained here show that MLs have highly sensitive T2/T2* MR contrast and can be successfully used for prelabeling or cells/ islets and subsequent in vivo imaging. MLs express lower level of toxic effects compared to other iron oxide particles (2) and functionalized MLs using cell recognizing ligands such as peptides (e.g. cRGD peptide), small molecules (e.g. lactose moieties) and vitamins (e.g vitamin A) were already validate by our group for the in vitro and in vivo visualization of hepatocytes and hepatic setellate cells, respectively (3). The later were used for the early detection of liver fibrosis. The focus of our future work is on in vivo targeting of beta cells for diabetes therapy using molecules that target receptors of beta cells, including the GPR-40 receptor using a thio-derivative of TAK-875, a potent GPR-40 agonist
Publication status: accepted
KU Leuven publication type: AMa
Appears in Collections:Biomedical MRI

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