Hundshammer Christian, Düwel Stephan, Köcher Simone S, Gersch Malte, Feuerecker Benedikt, Scheurer Christoph, Haase Axel, Glaser Steffen J, Schwaiger Markus, Schilling Franz
Department of Nuclear Medicine, Klinikum rechts der Isar, Technical University of Munich, Ismaninger Str. 22, 81675, München, Germany.
Department of Chemistry, Technical University of Munich, Lichtenbergstr. 4, 85748, Garching, Germany.
Chemphyschem. 2017 Sep 20;18(18):2422-2425. doi: 10.1002/cphc.201700779. Epub 2017 Aug 17.
Aberrant pH is characteristic of many pathologies such as ischemia, inflammation or cancer. Therefore, a non-invasive and spatially resolved pH determination is valuable for disease diagnosis, characterization of response to treatment and the design of pH-sensitive drug-delivery systems. We recently introduced hyperpolarized [1,5- C ]zymonic acid (ZA) as a novel MRI probe of extracellular pH utilizing dissolution dynamic polarization (DNP) for a more than 10000-fold signal enhancement of the MRI signal. Here we present a strategy to enhance the sensitivity of this approach by deuteration of ZA yielding [1,5- C , 3,6,6,6-D ]zymonic acid (ZA ), which prolongs the liquid state spin lattice relaxation time (T ) by up to 39 % in vitro. Measurements with ZA and ZA on subcutaneous MAT B III adenocarcinoma in rats show that deuteration increases the signal-to-noise ratio (SNR) by up to 46 % in vivo. Furthermore, we demonstrate a proof of concept for real-time imaging of dynamic pH changes in vitro using ZA , potentially allowing for the characterization of rapid acidification/basification processes in vivo.
异常的pH值是许多病理状态的特征,如局部缺血、炎症或癌症。因此,非侵入性且具有空间分辨能力的pH值测定对于疾病诊断、治疗反应的表征以及pH敏感药物递送系统的设计具有重要价值。我们最近引入了超极化的[1,5-¹³C]zymonic酸(ZA)作为一种新型的细胞外pH值MRI探针,利用溶解动态极化(DNP)使MRI信号增强超过10000倍。在此,我们提出一种策略,通过对ZA进行氘代得到[1,5-¹³C,3,6,6,6-D₄]zymonic酸(ZA₄)来提高这种方法的灵敏度,其在体外可使液态自旋晶格弛豫时间(T₁)延长高达39%。用ZA和ZA₄对大鼠皮下MAT B III腺癌进行测量表明,氘代在体内可使信噪比(SNR)提高高达46%。此外,我们展示了使用ZA₄对体外动态pH值变化进行实时成像的概念验证,这可能允许对体内快速酸化/碱化过程进行表征。