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Radical dendrimers based on biocompatible oligoethylene glycol dendrimers as contrast agents for MRI

AuthorsZhang, Songbai; Lloveras, Vega ; Pulido, Daniel; Liko, Flonja; Pinto, Luiz Fernando; Albericio, Fernando; Royo, Miriam ; Vidal Gancedo, José
KeywordsContrast agent
Magnetic resonance imaging (MRI)
Organic radicals
OEG dendrimers
Radical dendrimers
Infectious diseases
Issue Date14-Aug-2020
PublisherMultidisciplinary Digital Publishing Institute
CitationPharmaceutics 12(8): 772 (2020)
AbstractFinding alternatives to gadolinium (Gd)-based contrast agents (CA) with the same or even better paramagnetic properties is crucial to overcome their established toxicity. Herein we describe the synthesis and characterization of entirely organic metal-free paramagnetic macromolecules based on biocompatible oligoethylene glycol dendrimers fully functionalized with 5 and 20 organic radicals (OEG Gn-PROXYL (n = 0, 1) radical dendrimers) with the aim to be used as magnetic resonance imaging (MRI) contrast agents. Conferring high water solubility on such systems is often a concern, especially in large generation dendrimers. Our approach to overcome such an issue in this study is by synthesizing dendrimers with highly water-soluble branches themselves. In this work, we show that the highly water-soluble OEG Gn-PROXYL (n = 0, 1) radical dendrimers obtained showed properties that convert them in good candidates to be studied as contrast agents for MRI applications like diagnosis and follow-up of infectious diseases, among others. Importantly, with the first generation radical dendrimer, a similar r1 relaxivity value (3.4 mM−1s−1) in comparison to gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) used in clinics (3.2 mM−1s−1, r.t. 7T) has been obtained, and it has been shown to not be cytotoxic, avoiding the toxicity risks associated with the unwanted accumulation of Gd in the body.
Publisher version (URL)https://doi.org/10.3390/pharmaceutics12080772
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