In Vivo Maps of Extracellular pH in Murine Melanoma by CEST–MRI

Purpose: A novel method based on the use of Yb-HPDO3A as MRI Para-CEST agent for in vivo pH mapping of the tumor region in a melanoma murine model is reported. This method does not require the knowledge of the concentration of the imaging agent. Methods: C57BL/6-mice were inoculated with B16-F10 cells. CEST–MR images of tumor and bladder were acquired upon the i.v. administration of Yb-HPDO3A (1.2 mmol/Kg). pH was assessed by the use of a ratiometric method. Results: Yb-HPDO3A distributes well in the extracellular space of the tumor allowing the detection of good levels of saturation transfer (ST). It is excreted throughout kidneys and accumulated in the bladder thus yielding a strong CEST signal from urine. By comparing the ST% obtained upon selective irradiation of the two AOH resonances belonging to the two isomeric forms of Yb-HPDO3A, it has been possible to measure the extracellular pH for each voxel (0.22 mm3). The obtained pH-maps of tumors show a great heterogeneity. Marked differences are associated to tumor staging. Conclusion: The application of Yb-HPDO3A to measure extracellular tumor pH provides a good spatio-temporal resolution and it does not require the prior knowledge of the contrast agent concentration. The herein reported data support the potential clinical translation of Yb-HPDO3A.