Facile Synthesis of Weakly Ferromagnetic Organogadolinium Macrochelates‐Based T(1)‐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(3+) and macromolecules is proposed. A library of macromolecules were screened for Gd(3+) 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. Gd(3+) 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.