Chelator-free Radiolabeling of Iron Oxide Nanoparticles with 68Ga for Dual Modality PET/MR Imaging (#102)
Radiolabeled magnetic nanoparticles, as dual-modality imaging agents, can be used in a number of diagnostic applications, since they combine the advantages of both PET and MR Imaging. In this study, a class of magnetic nanoparticles (NPs), radiolabeled with the positron emitting radionuclide 68Ga (t1/2=67,8min), is described. The aim of the present work was the radiolabeling of magnetite iron oxide nanoparticles in the absence of a chelating unit, and their consequent evaluation, using in vitro and in vivo methods.
Colloidal magnetic nanoparticles were prepared through arrested precipitation of magnetite, in presence of the coating polymer poly(methacrylic acid)-graft-polyethyleneglycolmethacrylate (PMMA-g-PEGMA). The radiolabeling procedure was conducted by incubating a mixture containing 68GaCl3 and NPs in Sodium Acetate Buffer (pH 4) at 70 °C. Samples were analyzed for radioactivity incorporation by Thin Layer Chromatography (TLC). Stability of the 68Ga-NPs was assessed in human plasma and fetal bovine serum (FBS) at 37 °C, up to 120 minutes post-labeling. In vitro cytotoxicity studies, using the MTT assay, were conducted on normal HEK293T cells and on the mouse mammary carcinoma 4T1 cell line. In vivo studies, including biodistribution of the 68Ga labeled NPs in normal mice models and athymic mice models bearing 4T1 tumor xenografts, were also performed.
Radiolabeling of chelator-free magnetic nanoparticles with 68Ga, resulted in high radiolabeling efficiency (>94%, 30 minutes post labeling) and stable complexes in biological fluids. Concentration‐dependent toxicity in the mouse mammary carcinoma 4T1 cell line was observed, with high viability in normal HEK293 cells. Satisfactory in vivo behavior in normal mice and 4T1 tumor‐bearing mice models prompt us to further investigate this radiotracer for use as a potential dual-modality PET/MR imaging agent.
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