Radical Dendrimers Based on Biocompatible Oligoethylene Glycol Dendrimers as Contrast Agents for MRI

Songbai Zhang; Vega Lloveras; Daniel Pulido; Flonja Liko; Luiz F Pinto; Fernando Albericio; Miriam Royo; José Vidal-Gancedo

doi:10.3390/pharmaceutics12080772

Radical Dendrimers Based on Biocompatible Oligoethylene Glycol Dendrimers as Contrast Agents for MRI

Pharmaceutics. 2020 Aug 14;12(8):772. doi: 10.3390/pharmaceutics12080772.

Authors

Songbai Zhang¹, Vega Lloveras¹, Daniel Pulido², Flonja Liko¹, Luiz F Pinto¹, Fernando Albericio^{2

3

4}, Miriam Royo², José Vidal-Gancedo¹

Affiliations

¹ Institut de Ciència de Materials de Barcelona (ICMAB-CSIC) and CIBER-BBN, Campus Universitari de Bellaterra, Bellaterra, 08193 Barcelona, Spain.
² Institut de Química Avançada de Catalunya (IQAC-CSIC) and CIBER-BBN c/ Jordi Girona 18-26, 08034 Barcelona, Spain.
³ Department of Inorganic and Organic Chemistry, University of Barcelona, 08028 Barcelona, Spain.
⁴ School of Chemistry and Physics, University of KwaZulu-Natal, Durban 4041, South Africa.

Abstract

Finding 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.

Keywords: Gd-DTPA; OEG dendrimers; PROXYL; contrast agent; infectious diseases; magnetic resonance imaging (MRI); organic radicals; radical dendrimers; relaxivity.