Versolatto Silvia, Boccalon Mariangela, Guidolin Nicol, Travagin Fabio, Alessio Enzo, Aime Silvio, Balducci Gabriele, Giovenzana Giovanni B, Baranyai Zsolt
Dipartimento di Scienze Chimiche e Farmaceutiche Università di Trieste, Piazzale Europa 1, 34127, Trieste, TS, Italy.
Bracco Imaging Spa, CRB Trieste, AREA Science Park, 34149, Basovizza, TS, Italy.
Chemistry. 2024 May 17;30(28):e202400344. doi: 10.1002/chem.202400344. Epub 2024 Apr 4.
[Gd(HP-DO3A)] (gadoteridol) as an active compound of ProHance is a widely employed contrast agent in clinical MRI scans in the last 30 years. Recent concerns about the long-term retention of gadolinium-based contrast agents (GBCAs) led to a deeper investigation of the structural features underlying the integrity of the paramagnetic metal complex. Several human and nonclinical studies have noted marked differences among the macrocyclic GBCAs, with the least retention of Gd traces and most rapid elimination consistently being reported for [Gd(HP-DO3A)]. It was deemed of interest to assess how minor structural/electronic changes associated to the ligand structure may affect basic properties of the metal complex with several [Gd(HP-DO3A)] analogues synthesized and characterized in the last years. We recently reported that the closest homolog of [Gd(HP-DO3A)], i. e.: [Gd(HB-DO3A)], in which a (±)-2-hydroxy-1-propyl pendant arm is replaced by a (±)-2-hydroxy-1-butyl moiety, showed a significantly different retention behaviour in the model interaction with collagen, despite the apparently very minor structural difference. In this paper we report a comprehensive study of the structural, thermodynamic, kinetic and relaxation properties of [Gd(HB-DO3A)], compared to the parent [Gd(HP-DO3A)] and to other closely related macrocyclic GBCAs to assess whether very minor structural changes can modulate the physico-chemical properties of Gd complexes.
钆特醇（[Gd(HP-DO3A)]）作为普乐显（ProHance）的活性成分，是过去30年临床磁共振成像（MRI）扫描中广泛使用的造影剂。最近，人们对基于钆的造影剂（GBCAs）的长期留存问题表示担忧，这促使人们更深入地研究顺磁性金属配合物完整性背后的结构特征。多项人体和非临床研究指出，大环GBCAs之间存在显著差异，对于[Gd(HP-DO3A)]，一直有报道称其钆痕量留存最少且消除最快。近年来合成并表征了几种[Gd(HP-DO3A)]类似物，评估与配体结构相关的微小结构/电子变化如何影响金属配合物的基本性质被认为很有意义。我们最近报道，[Gd(HP-DO3A)]最接近的同系物，即[Gd(HB-DO3A)]，其中(±)-2-羟基-1-丙基侧链被(±)-2-羟基-1-丁基部分取代，尽管结构差异看似很小，但在与胶原蛋白的模型相互作用中表现出显著不同的留存行为。在本文中，我们报告了对[Gd(HB-DO3A)]的结构、热力学、动力学和弛豫性质的全面研究，并与母体[Gd(HP-DO3A)]以及其他密切相关的大环GBCAs进行比较，以评估非常微小的结构变化是否能调节钆配合物的物理化学性质。
