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Kilogram scale facile synthesis and systematic characterization of a Gd-macrochelate as T₁-weighted magnetic resonance imaging contrast agent.

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 r₂/r₁ ratio of the reported Gd macrochelates that is an important factor for T₁ 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 r₁ value of 16.35 mM^-1 s^-1 and r₂/r₁ 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.

SUBMITTER: Shi M

PROVIDER: S-EPMC11005285 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature

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Kilogram scale facile synthesis and systematic characterization of a Gd-macrochelate as T1-weighted magnetic resonance imaging contrast agent.

Shi Meng M Xiong Wei W Feng Jie J Wu Lihe L Yang Jing J Lu Yudie Y Lu Xuanyi X Fan Qingdeng Q Nie Hemin H Dai Yunlu Y Yan Chenggong C Tian Ye Y Shen Zheyu Z

Journal of nanobiotechnology 20240409 1

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 r2/r1 ratio of the reported Gd macrochelates that is an important factor for T1 imaging, in this study, a superior macromolecule hydrolyzed polymaleic anhydride (HPM ...[more]

PMID: 38594700

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Project description:BackgroundMRI is very important for guiding the diagnosis and treatment of brachial plexus diseases. The most used type of MRI brachial plexus imaging is the 3D Short Term Inversion Recovery (STIR) sequence with contrast agent. This study aimed to investigate the effect of three contrast agents; gadobenate dimeglumine (Gd-BOPTA), gadopentetate dimeglumine (Gd-DTPA), and Gadoteric Acid Meglumine (Gd-DOTA) on brachial plexus magnetic resonance imaging (MRI).MethodsWe recruited 60 patients with suspected brachial plexus injury randomly into three groups. MRI images were obtained from each patient. Prior to scanning, the first group was injected with GD-BOPTA, the second group with Gd-DTPA, and the third with Gd-DOTA. The amount of contrast agent was 0.1 mmol/kg according to the weight of each patient, the injection rate was 1.5 mL/s, and 20 mL saline was injected at the same rate with a high-pressure injector. Immediately after the injection of contrast agent and saline, a 3D Sampling perfection with application optimized contrasts using different flip angle evolutions (SPACE) STIR sequence was used for scanning. The Signal Intensity (SI) and Standard Deviation (SD) of Maximal intensity projection (MIP) images for regions outside the anatomy (ROI background) with area of 17 mm2 on both sides of the C6 peripheral nerves (ROI nerve), and tissue adjacent to the peripheral nerves (ROI tissue) were obtained. Signal to noise ratio (SNR) and contrast to noise ratio (CNR) were then calculated.ResultsThe SNR was 40.66±25.27, 34.65±14.86, and 44.63±30.79 for Gd-BOPTA, Gd-DTPA, and Gd-DOTA, respectively and the CNR was 20.24±15.17, 16.07±7.50, and 20.84±15.53 for Gd-BOPTA, Gd-DTPA, and Gd-DOTA, respectively. In addition, there was no statistical difference in the SNR or CNR of brachial plexus nerves using the three contrast agents to enhance the 3D SPACE sequence χ2=1.877, P=0.391>0.05 and χ2=1.717, P=0.424, respectively.ConclusionsThere were no significant differences in the efficacy of three contrast agents in imaging the brachial plexus.

Dataset Information

Kilogram scale facile synthesis and systematic characterization of a Gd-macrochelate as T₁-weighted magnetic resonance imaging contrast agent.

Publications

Kilogram scale facile synthesis and systematic characterization of a Gd-macrochelate as T<sub>1</sub>-weighted magnetic resonance imaging contrast agent.

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