Transmembrane pH gradient imaging in rodent glioma models

Area of Science:

• Oncology
• Biophysics
• Medical Imaging

Background:

• Tumor microenvironments exhibit extracellular acidosis due to metabolic reprogramming and H+ ion overproduction.
• The transmembrane pH gradient (ΔpH) is greater in tumors than normal tissues, influencing drug delivery and therapeutic targeting.
• Current methods for assessing ΔpH lack the resolution required for detailed tumor analysis.

Purpose of the Study:

• To develop and validate a novel MRI/MRSI-based technique for high-resolution ΔpH imaging in gliomas.
• To quantify the ΔpH in experimental rat and mouse glioma models.
• To establish a platform for in vivo ΔpH assessment in brain tumors.

Main Methods:

• Development of a submillimeter-resolution MRI/MRSI technique for ΔpH imaging.
• Measurement of intracellular pH (pHi) using Amine and Amide Concentration-Independent Detection (AACID).
• Measurement of extracellular pH (pHe) using Biosensor Imaging of Redundant Deviation in Shifts (BIRDS).
• Application of the technique to RG2, U87, and GL261 glioma models in rats and mice.

Main Results:

• Intracellular pH (pHi) was slightly higher in tumors (7.40-7.47) compared to normal brain (7.30-7.38).
• Extracellular pH (pHe) was significantly lower in tumors (6.62-6.84) compared to normal brain (7.17-7.21).
• Tumors exhibited a significantly higher ΔpH (0.62-0.81) compared to normal brain (0.13-0.16).

Conclusions:

• The developed MRI/MRSI platform enables submillimeter resolution ΔpH imaging in gliomas.
• The study confirms a larger ΔpH in tumor tissues, consistent with metabolic reprogramming.
• This technique offers a promising tool for investigating tumor biology and guiding cancer therapy.