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Kilogram scale facile synthesis and systematic characterization of a Gd-macrochelate as T1-weighted magnetic resonance imaging contrast agent
- Source :
- Journal of Nanobiotechnology, Vol 22, Iss 1, Pp 1-15 (2024)
- Publication Year :
- 2024
- Publisher :
- BMC, 2024.
-
Abstract
- Abstract To overcome the problems of commercial magnetic resonance imaging (MRI) contrast agents (CAs) (i.e., small molecule Gd chelates), we have proposed a new concept of Gd macrochelates based on the coordination of Gd3+ and macromolecules, e.g., poly(acrylic acid) (PAA). To further decrease the r 2/r 1 ratio of the reported Gd macrochelates that is an important factor for T 1 imaging, in this study, a superior macromolecule hydrolyzed polymaleic anhydride (HPMA) was found to coordinate Gd3+. The synthesis conditions were optimized and the generated Gd-HPMA macrochelate was systematically characterized. The obtained Gd-HPMA29 synthesized in a 100 L of reactor has a r 1 value of 16.35 mM−1 s−1 and r 2/r 1 ratio of 2.05 at 7.0 T, a high Gd yield of 92.7% and a high product weight (1074 g), which demonstrates the feasibility of kilogram scale facile synthesis. After optimization of excipients and sterilization at a high temperature, the obtained Gd-HPMA30 formulation has a pH value of 7.97, osmolality of 691 mOsmol/kg water, density of 1.145 g/mL, and viscosity of 2.2 cP at 20 ℃ or 1.8 cP at 37 ℃, which meet all specifications and physicochemical criteria for clinical injections indicating the immense potential for clinical applications. Graphical Abstract
Details
- Language :
- English
- ISSN :
- 14773155
- Volume :
- 22
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- Journal of Nanobiotechnology
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.26466d6c6212429f975df70f55fc70a1
- Document Type :
- article
- Full Text :
- https://doi.org/10.1186/s12951-024-02394-8