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

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 Gd and macromolecules is proposed. A library of macromolecules were screened for Gd 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 -weighted CAs owing to their super high r values (> 50 mm  s , 3.0 T) and ultralow r /r 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  < 1.0 emu g ) leading to a low r , which is preferred for T MRI. Gd is not released from the OGMC Gd-PAA12 and Gd-PASP11, ensuring biosafety for in vivo applications. The safety and T -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 -weighted CAs with promising translatability to replace the commercial Gd chelates.