Facile Synthesis of Weakly Ferromagnetic Organogadolinium Macrochelates-Based T1-Weighted Magnetic Resonance Imaging Contrast Agents

초록

To surmount the major concerns of commercial small molecule Gd chelates and reported Gd-based contrast agents (GBCAs) for magnetic resonance imaging (MRI), a new concept of organogadolinium macrochelates (OGMCs) constructed from the coordination between Gd3+ and macromolecules is proposed. A library of macromolecules were screened for Gd3+ coordination, and two candidates [i.e., poly(acrylic acid) (PAA), and poly(aspartic acid) (PASP)] succeeded in OGMC formation. Under optimized synthesis conditions, both Gd-PAA12 and Gd-PASP11 OGMCs are outstanding T-1-weighted CAs owing to their super high r(1) values (> 50 mm(-1) s(-1), 3.0 T) and ultralow r(2)/r(1) ratios (< 1.6, 3.0 T). The ferromagnetism of OGMCs is completely different from the paramagnetism of commercial and reported GBCAs. The ferromagnetism is very weak (M-s < 1.0 emu g(-1)) leading to a low r(2), which is preferred for T-1 MRI. Gd3+ is not released from the OGMC Gd-PAA12 and Gd-PASP11, ensuring biosafety for in vivo applications. The safety and T-1-weighted MRI efficiencies of the OGMC Gd-PAA12 and Gd-PASP11 are tested in cells and mice. The synthesis method of the OGMCs is facile and easy to be scaled up. Consequently, the OGMC Gd-PAA12 and Gd-PASP11 are superior T-1-weighted CAs with promising translatability to replace the commercial Gd chelates.

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