Gas-phase synthesis of gadolinium nanoparticles for magnetic resonance imaging contrast agents
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Gadolinium ions are the paramagnetic component of the most common intravenous contrast agents for medical magnetic resonance imaging (MRI). Because gadolinium ions are toxic, these MRI contrast agents include chelating agents that bind the gadolinium ion strongly. Five such agents are FDA approved. Unfortunately, all of them are the subject of recent FDA rulings that impose new labeling requirements, due to patients with severely impaired kidneys developing a rare but potentially fatal disease called Nephrogenic Systemic Fibrosis, which is linked to gadolinium exposure. Pure gadolinium or gadolinium oxide nanoparticles, with proper encapsulation, may provide a safer and equally or more effective alternative to chelated gadolinium ions in this application. The High Temperature Reducing Jet (HTRJ) process is a novel flame based aerosol synthesis method that can produce metal nanoparticles with a thin carbon coating in a single step. Carbon-coated gadolinium and gadolinium oxide nanoparticles have been synthesized in this reactor system. The surface of these nanoparticles was modified with dextran and other biocompatible molecules to enable their dispersion in water and biological media. The resulting nanoconstructs were characterized by TEM, SEM/EDS, XRD, Raman spectroscopy, TGA, and DSC. Most importantly, their T1 relaxivity was measured to determine their potential for use in MRI contrast enhancement. Sensitive colorimetric chemical assays for gadolinium ions were used to monitor release of gadolinium ions. The High Temperature Reducing Jet (HTRJ) reactor system may also be able to produce low reduction potential metal nanoparticles. Magnesium-containing nanoparticles were synthesized in order to be used as a master comparison with the gadolinium-containing nanoparticles. The resulting metal and metal oxide particles were characterized by TEM, SEM/EDS, and XRD and their size, morphology, chemical composition, and stability were compared against the gadolinium nanoparticles.