Paranawithana Namini N, Chiaffarelli Remy, Kretschmer Jan, Buchanan Emily, Lopez Katherine, Zhao Piyu, Kiefer Garry, Jurek Paul, Martins André F, Sherry A Dean
Department of Chemistry and Biochemistry, The University of Texas at Dallas, Richardson, Texas 75080, United States.
Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University of Tübingen, Tübingen 72076, Germany.
Inorg Chem. 2024 Mar 4;63(9):4072-4077. doi: 10.1021/acs.inorgchem.3c03639. Epub 2024 Feb 22.
This study was designed to test whether the single appended phosphonate group in GdDOTA-1AmP is sufficient for catalyzing the exchange of proton from the single inner-sphere water-exchanging molecule. Unlike the other phosphonate derivatives in this series, GdDOTA-1AmP showed a surprisingly smooth increase in relaxivity from 3.0 to 6.3 mM s at 20 MHz as the pH was lowered from 9 to 2.5. In comparison to the bis-, tris-, and tetrakis-phosphonate analogues, which all show a biphasic dependence of with changes in pH, the unique versus pH characteristics of GdDOTA-1AmP are shown to closely parallel deprotonation of the single appended phosphonate group. Although the tissue biodistribution and clearance rates of GdDOTA-1AmP are more favorable than the other more highly charged phosphonate derivatives, the pH dependency of is substantially reduced at magnetic fields typically used for small animal imaging (7 and 9.4T), so the attractiveness of this new molecule for quantitative imaging of tissue pH is diminished. However, this study provides some new insights into the feasibility of designing pH-responsive MRI contrast agents based upon fundamental acid-base prototropic mechanisms.
本研究旨在测试钆喷酸葡胺-1AmP（GdDOTA-1AmP）中单个附加的膦酸基团是否足以催化单个内球水交换分子中质子的交换。与该系列中的其他膦酸衍生物不同，当pH值从9降至2.5时，GdDOTA-1AmP在20 MHz下的弛豫率从3.0增至6.3 mM/s，呈现出惊人的平稳增长。与双膦酸、三膦酸和四膦酸类似物相比，它们的弛豫率随pH变化均呈现双相依赖性，而GdDOTA-1AmP独特的弛豫率与pH特性显示出与单个附加膦酸基团的去质子化密切平行。尽管GdDOTA-1AmP的组织生物分布和清除率比其他电荷更高的膦酸衍生物更有利，但在通常用于小动物成像的磁场（7和9.4T）下，其弛豫率对pH的依赖性显著降低，因此这种新分子用于组织pH定量成像的吸引力减弱。然而，本研究为基于基本酸碱质子转移机制设计pH响应性磁共振成像造影剂的可行性提供了一些新见解。
