在这里，我们描述和评估了14种新合成的咪唑-4,5-二羧酰胺（I45DCs）在pH和灌注成像中的潜力。这些芳香化合物中有很多具有较大的活性质子化学位移（高达从水7.7 ppm）由于它们的分子内氢键和第二个活性质子，以允许化学交换饱和转移（CEST）信号比基础的pH测量。我们发现对于一系列的取代产生的对比度强，可根据这些取代来调整CEST信号比与pH图之间的拐点，以生成无浓度依赖的pH图。这些I45DC CEST剂在肿瘤和肾pH映射中具有优势，不仅在临床前和初步人体研究中，而且随着CEST MRI与外源性对比剂结合的能力能够检测肾脏的功能性变化，我们评估了我们表现最好的阴离子化合物（I45DC-diGlu）在单侧尿路梗阻小鼠模型上，并观察到梗阻肾脏的对比度摄取较低，而非梗阻肾脏则显示pH约为6.5，而梗阻肾脏的pH升高且pH值范围增加。基于此，我们得出结论，I45DC具有出色的成像特性，并具有在各种医学成像应用，尤其是肾脏成像方面的前景。 ©2022 John Wiley＆ Sons Ltd.

Here, we describe and assess the potential of 14 newly synthesized imidazole-4,5-dicarboxyamides (I45DCs) for pH and perfusion imaging. A number of these aromatic compounds possess large labile proton chemical shifts (up to 7.7 ppm from water) because of their intramolecular hydrogen bonds and a second labile proton to allow for chemical exchange saturation transfer (CEST) signal ratio-based pH measurements. We have found that the contrast produced is strong for a wide range of substitutions and that the inflection points in the CEST signal ratio versus pH plots used to generate concentration-independent pH maps can be adjusted based on these subsitutions to tune the pH range that can be measured. These I45DC CEST agents have advantages over the triiodobenzenes currently employed for tumor and kidney pH mapping, both preclinically and in initial human studies. Finally, as CEST MRI combined with exogenous contrast has the potential to detect functional changes in the kidneys, we evaluated our highest performing anionic compound (I45DC-diGlu) on a unilateral urinary obstruction mouse model and observed lower contrast uptake in the obstructed kidney compared with the unobstructed kidney and that the unobstructed kidney displayed a pH of ~ 6.5 while the obstructed kidney had elevated pH and an increased range in pH values. Based on this, we conclude that the I45DCs have excellent imaging properties and hold promise for a variety of medical imaging applications, particularly renal imaging.© 2022 John Wiley & Sons Ltd.