Chiral Gd-DOTA as a Versatile Platform for Hepatobiliary and Tumor Targeting MRI Contrast Agents

The leakage of gadolinium ions (Gd3+) from
commercial
Gd3+-based contrast agents (GBCAs) in patients is currently
the major safety concern in clinical magnetic resonance imaging (MRI)
scans, and the lack of task-specific GBCAs limits its usage in the
early detection of disease and imaging of specific biological regions.
Herein, ultrastable GBCAs were constructed via decorating chiral Gd-DOTA
with a phenylic analogue to one of the pendent arms, and the stability
constant was determined as high as 27.08, accompanied by negligible
decomplexation in 1 M of HCl over 2 years. A hepatic-specific chiral
Gd-DOTA was screened out as a potential alternative to commercial
Gd-EOB-DTPA, while combination with functional molecules favored chiral
Gd-DOTA as tumor targeting probes. Therefore, the novel chiral Gd-DOTA
is believed to be an ideal platform for designing the next generation
of GBCAs for various clinical purposes due to its outstanding inert
nature.

目前，在临床磁共振成像（MRI）扫描中，从基于钆(Gd3+)的商业对比剂（GBCAs）中泄漏的钆离子（Gd3+）已成为主要的临床安全关注点，而缺乏特定任务用的GBCAs限制了其在疾病早期检测和特定生物学区域成像中的应用。本研究中，通过在具有手征性的Gd-DOTA分子上修饰苯基类似物于其侧链之一，构建了超稳定性的GBCAs，其稳定性常数为27.08，在2年的时间内，即使在1 M的HCl溶液中，其去复合也微乎其微。一种针对肝脏特异性的手征性Gd-DOTA被筛选出来，作为商业Gd-EOB-DTPA的潜在替代品，而与功能性分子的结合则更倾向于将手征性Gd-DOTA作为肿瘤靶向探针。因此，鉴于其卓越的惰性性质，新型的手征性Gd-DOTA被认为是为各种临床目的设计下一代GBCAs的理想平台。