(23)Na‐MRI as a Noninvasive Biomarker for Cancer Diagnosis and Prognosis

The influx of sodium (Na(+)) ions into a resting cell is regulated by Na(+) channels and by Na(+)/H(+) and Na(+)/Ca(2+) exchangers, whereas Na(+) ion efflux is mediated by the activity of Na(+)/K(+)‐ATPase to maintain a high transmembrane Na(+) ion gradient. Dysfunction of this system leads to changes in the intracellular sodium concentration that promotes cancer metastasis by mediating invasion and migration. In addition, the accumulation of extracellular Na(+) ions in cancer due to inflammation contributes to tumor immunogenicity. Thus, alterations in the Na(+) ion concentration may potentially be used as a biomarker for malignant tumor diagnosis and prognosis. However, current limitations in detection technology and a complex tumor microenvironment present significant challenges for the in vivo assessment of Na(+) concentration in tumor. (23)Na‐magnetic resonance imaging ((23)Na‐MRI) offers a unique opportunity to study the effects of Na(+) ion concentration changes in cancer. Although challenged by a low signal‐to‐noise ratio, the development of ultrahigh magnetic field scanners and specialized sodium acquisition sequences has significantly advanced (23)Na‐MRI. (23)Na‐MRI provides biochemical information that reflects cell viability, structural integrity, and energy metabolism, and has been shown to reveal rapid treatment response at the molecular level before morphological changes occur. Here we review the basis of (23)Na‐MRI technology and discuss its potential as a direct noninvasive in vivo diagnostic and prognostic biomarker for cancer therapy, particularly in cancer immunotherapy. We propose that (23)Na‐MRI is a promising method with a wide range of applications in the tumor immuno‐microenvironment research field and in cancer immunotherapy monitoring. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2