CEST-MRI for glioma pH quantification in mouse model: Validation by immunohistochemistry

Area of Science:

• Neuroimaging
• Biochemistry
• Oncology

Background:

• Glioma extracellular pH (pHe) acidification promotes tumor progression, including proliferation, angiogenesis, immunosuppression, invasion, and chemoresistance.
• Accurate quantification of glioma pHe is critical for understanding and treating these tumors.

Purpose of the Study:

• To apply the YbHPDO3A probe for in vivo glioma pHe quantification using chemical exchange saturation transfer (CEST)-MRI.
• To correlate in vivo pHe measurements with tumor metabolism assessed by immunohistochemistry.

Main Methods:

• U87 glioma mouse model (n=18) underwent MRI at 4.7T.
• CEST-MRI with YbHPDO3A probe was used for pHe mapping.
• T2w* sequences assessed YbHPDO3A biodistribution, and immunohistochemistry (Ki-67, CA-IX, NHE-1) evaluated tumor metabolism.

Main Results:

• CEST-MRI with YbHPDO3A successfully mapped glioma pHe, revealing a correlation between lower pH and higher proliferation (Ki-67).
• Acidic pHe regions (mean 6.6) showed significantly higher expression of CA-IX and NHE-1 compared to higher pH regions (mean 7.00).
• Immunohistochemical results strongly correlated with pHe mapping (Pearson correlation coefficient > 0.70).

Conclusions:

• CEST-MRI with the YbHPDO3A probe is a feasible method for in vivo glioma pHe quantification at 4.7T.
• The YbHPDO3A probe, similar to GdHPDO3A, shows promise for clinical translation in glioma imaging.
• This technique provides insights into the acidic and hypoxic microenvironment of gliomas, correlating with tumor aggressiveness.