Zhang Junhui, Dai Lixiong, He Li, Bhattarai Abhisek, Chan Chun-Ming, Tai William Chi-Shing, Vardhanabhuti Varut, Law Ga-Lai
State Key Laboratory of Chemical Biology and Drug Discovery, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Hong Kong SAR, China.
The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen, 518000, China.
Commun Chem. 2023 Nov 16;6(1):251. doi: 10.1038/s42004-023-01050-w.
Due to the adverse effects of de-metallation in past concerning FDA-approved gadolinium-based contrast agents (GBCAs), researchers have been focusing on developing safer and more efficient alternatives that could avoid toxicity caused by free gadolinium ions. Herein, two chiral GBCAs, Gd-LS with sulfonate groups and Gd-T with hydroxyl groups, are reported as potential candidates for magnetic reasonance imaging (MRI). The r relaxivities of TSAP, SAP isomers of Gd-LS and SAP isomer of Gd-T at 1.4 T, 37 °C in water are 7.4 mMs, 14.5 mMs and 5.2 mMs, respectively. Results show that the hydrophilic functional groups introduced to the chiral macrocyclic scaffold of Gd-T and Gd-LS both give constructive influences on the second-sphere relaxivity and enhance the overall r value. Both cases indicate that the design of GBCAs should also focus on the optimal window in Solomon-Bloembergen-Morgan (SBM) theory and the effects caused by the second-sphere and outer-sphere relaxivity.
由于过去美国食品药品监督管理局（FDA）批准的钆基造影剂（GBCAs）存在脱金属的不良影响，研究人员一直致力于开发更安全、更有效的替代品，以避免游离钆离子引起的毒性。在此，报告了两种手性GBCAs，即具有磺酸基团的Gd-LS和具有羟基的Gd-T，作为磁共振成像（MRI）的潜在候选物。Gd-LS的TSAP、SAP异构体以及Gd-T的SAP异构体在1.4 T、37°C水中的弛豫率分别为7.4 mM⁻¹s⁻¹、14.5 mM⁻¹s⁻¹和5.2 mM⁻¹s⁻¹。结果表明，引入到Gd-T和Gd-LS手性大环支架上的亲水性官能团均对第二配位层弛豫率产生建设性影响，并提高了整体弛豫率值。两种情况均表明，GBCAs的设计还应关注所罗门-布洛姆伯根-摩根（SBM）理论中的最佳窗口以及第二配位层和外层弛豫率所产生的影响。
