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

Yudie Lu; Zhiyu Liang; Jie Feng; Lin Huang; Shuai Guo; Peiwei Yi; Wei Xiong; Sijin Chen; Sugeun Yang; Yikai Xu; Yan Li; Xiaoyuan Chen; Zheyu Shen

doi:10.1002/advs.202205109

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

Adv Sci (Weinh). 2022 Nov 15;10(1):e2205109. doi: 10.1002/advs.202205109. Online ahead of print.

Authors

Yudie Lu¹, Zhiyu Liang², Jie Feng², Lin Huang¹, Shuai Guo¹, Peiwei Yi¹, Wei Xiong², Sijin Chen², Sugeun Yang³, Yikai Xu², Yan Li¹, Xiaoyuan Chen⁴, Zheyu Shen^{1

2}

Affiliations

¹ School of Biomedical Engineering, Southern Medical University, Guangzhou, Guangdong, 510515, China.
² Medical Imaging Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China.
³ Department of Biomedical Science, BK21 FOUR Program in Biomedical Science and Engineering, Inha University College of Medicine, Incheon, 22212, South Korea.
⁴ Departments of Diagnostic Radiology, Surgery, Chemical and Biomolecular Engineering, and Biomedical Engineering, Clinical Imaging Research Centre, Nanomedicine Translational Research Program, Yong Loo Lin School of Medicine and Faculty of Engineering, National University of Singapore, Singapore, 119228, Singapore.

Abstract

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 T₁ -weighted CAs owing to their super high r₁ values (> 50 mm^-1 s^-1 , 3.0 T) and ultralow r₂ /r₁ 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 r₂ , which is preferred for T₁ MRI. Gd³⁺ is not released from the OGMC Gd-PAA12 and Gd-PASP11, ensuring biosafety for in vivo applications. The safety and T₁ -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 T₁ -weighted CAs with promising translatability to replace the commercial Gd chelates.

Keywords: hundred-gram-scale facile synthesis; magnetic resonance imaging (MRI) contrast agents (CAs); organogadolinium macrochelates (OGMCs); outstanding relaxivities; weak ferromagnetism.

Abstract

Grants and funding