AcidoCEST MRI Evaluates the Bone Microenvironment in Multiple Myeloma

Area of Science:

• Biomedical Imaging
• Oncology
• Metabolic Research

Background:

• Multiple myeloma (MM) is an incurable plasma cell malignancy.
• Hypoxia and decreased extracellular pH (pHe) are implicated in MM progression and drug resistance.
• Glucose transporters (GLUTs) are upregulated in hypoxic and cancerous cells.

Purpose of the Study:

• To evaluate the feasibility of acidoCEST MRI for measuring bone marrow pHe in an orthotopic mouse model of MM.
• To compare acidoCEST MRI-derived pHe measurements with GLUT1 immunofluorescence staining.

Main Methods:

• An orthotopic mouse model of MM was established using RPMI8226 cells.
• AcidoCEST MRI was performed on mice before and after contrast agent administration.
• Bone marrow pHe was calculated using Bloch-McConnell equations.
• Immunohistochemistry for GLUT1 was performed on decalcified bone marrow sections.

Main Results:

• A strong negative correlation was observed between pHe and GLUT1 expression (r = -0.75, p < 0.001).
• A strong positive correlation was found between [H3O+] and GLUT1 expression (r = 0.8, p < 0.001).
• AcidoCEST MRI successfully measured bone marrow pHe in the MM model.

Conclusions:

• AcidoCEST MRI is a feasible method for assessing bone marrow extracellular pH in multiple myeloma.
• The study demonstrates a strong correlation between acidoCEST MRI-derived pHe and GLUT1 expression, indicating its utility in assessing tumor metabolic phenotype.