Simultaneous magnetic resonance imaging of pH, perfusion and renal filtration using hyperpolarized ¹³C-labelled Z-OMPD

pH alterations are a hallmark of many pathologies including cancer and kidney disease. Here, we introduce [1,5-C-13(2)]Z-OMPD as a hyperpolarized extracellular pH and perfusion sensor for MRI which allows to generate a multiparametric fingerprint of renal disease status and to detect local tumor acidification. Exceptional long T-1 of two minutes at 1 T, high pH sensitivity of up to 1.9 ppm per pH unit and suitability of using the C-1-label as internal frequency reference enables pH imaging in vivo of three pH compartments in healthy rat kidneys. Spectrally selective targeting of both C-13-resonances enables simultaneous imaging of perfusion and filtration in 3D and pH in 2D within one minute to quantify renal blood flow, glomerular filtration rates and renal pH in healthy and hydronephrotic kidneys with superior sensitivity compared to clinical routine methods. Imaging multiple biomarkers within a single session renders [1,5-C-13(2)]Z-OMPD a promising new hyperpolarized agent for oncology and nephrology. pH alterations are a hallmark of many pathologies including cancer and kidney disease. Here the authors describe [1,5- 13 C2]Z-OMPD as a probe for hyperpolarized 13C-MRI with good pH sensitivity and hyperpolarization properties which combined with tailored MRI protocols allow sub-minute imaging of pH, renal perfusion and filtration simultaneously.