Department of Biotechnology, Delft University of Technology, Van der Maasweg 9, 2629 HZ Delft, The Netherlands.
Department of Science and Technological Innovation, Università del Piemonte Orientale, Viale Michel 11, 15121 Alessandria, Italy.
Molecules. 2021 Mar 19;26(6):1730. doi: 10.3390/molecules26061730.
It is known that phenylboronic acid (PBA) can target tumor tissues by binding to sialic acid, a substrate overexpressed by cancer cells. This capability has previously been explored in the design of targeting diagnostic probes such as Gd- and Ga-DOTA-EN-PBA, two contrast agents for magnetic resonance imaging (MRI) and positron emission tomography (PET), respectively, whose potential has already been demonstrated through in vivo experiments. In addition to its high resolution, the intrinsic low sensitivity of MRI stimulates the search for more effective contrast agents, which, in the case of small-molecular probes, basically narrows down to either increased tumbling time of the entire molecule or elevated local concentration of the paramagnetic ions, both strategies resulting in enhanced relaxivity, and consequently, a higher MRI contrast. The latter strategy can be achieved by the design of multimeric Gd complexes. Based on the monomeric PBA-containing probes described recently, herein, we report the synthesis and characterization of the dimeric analogues (Gd-DOTA-EN)-PBA and (Gd-DOTA-EN)FPBA. The presence of two Gd ions in one molecule clearly contributes to the improved biological performance, as demonstrated by the relaxometric study and cell-binding investigations.
已知苯硼酸（PBA）可以通过与癌细胞过度表达的唾液酸结合来靶向肿瘤组织。这一特性已在靶向诊断探针的设计中得到了探索，如 Gd 和 Ga-DOTA-EN-PBA，它们分别是磁共振成像（MRI）和正电子发射断层扫描（PET）的对比剂，其潜力已通过体内实验得到了证明。除了具有高分辨率外，MRI 的固有低灵敏度刺激了对更有效的对比剂的研究，对于小分子探针而言，这基本上可以归结为整个分子的旋转时间延长或顺磁离子的局部浓度升高，这两种策略都导致弛豫率提高，从而提高 MRI 对比度。后一种策略可以通过设计多聚体 Gd 配合物来实现。基于最近报道的含有单体 PBA 的探针，我们在此报告了二聚体类似物（Gd-DOTA-EN）-PBA 和（Gd-DOTA-EN）FPBA 的合成和表征。一个分子中存在两个 Gd 离子显然有助于改善生物学性能，这可以通过弛豫测量研究和细胞结合研究来证明。
