Functional imaging beyond anatomy: The emerging role of magnetic resonance spectroscopy and metabolic biomarkers in monitoring targeted cancer therapy
TL;DR
It is argued that the field is transitioning from proof-of-principle pharmacodynamic studies toward standardised, biomarker-guided adaptive therapy, and that the principal barriers — technical harmonisation, quantification standards and prospective validation — are now well defined and addressable.
Abstract
Anatomical imaging — measurements of tumour size on computed tomography or conventional magnetic resonance imaging (MRI) — remains the backbone of oncologic response assessment, yet it is structurally blind to the earliest events of treatment action. Targeted anticancer agents, by definition, act on specific molecular pathways whose blockade alters tumour metabolism within hours to days, long before any measurable change in tumour dimensions. Magnetic resonance spectroscopy (MRS) and spectroscopic imaging (MRSI) are uniquely positioned to capture these pharmacodynamic events non-invasively, repeatedly and without ionising radiation, by quantifying endogenous metabolites that report on membrane phospholipid turnover (total choline, phosphomonoesters), aerobic glycolysis (lactate), neuronal and tissue integrity (N-acetylaspartate, citrate), oncometabolite production (2-hydroxyglutarate in IDH-mutant glioma) and, with hyperpolarised 13C and deuterium (2H) tracers, real-time metabolic fluxes. This review synthesises the principles, biomarker repertoire and clinical evidence for MRS-based monitoring of targeted cancer therapy across glioma, breast, prostate and abdominal malignancies; examines how metabolic readouts document on-target pathway modulation for kinase, PI3K/AKT/mTOR, IDH, antiangiogenic and endocrine agents; surveys the maturing technologies of hyperpolarised 13C MRSI and deuterium metabolic imaging; and discusses the integration of MRS with multiparametric MRI, artificial intelligence and nanotheranostic drug development. We argue that the field is transitioning from proof-of-principle pharmacodynamic studies toward standardised, biomarker-guided adaptive therapy, and that the principal barriers — technical harmonisation, quantification standards and prospective validation — are now well defined and addressable. Functional imaging beyond anatomy, anchored in MRS-detectable metabolic biomarkers, offers a practical route to earlier response assessment, reduced exposure to ineffective therapy and more informative oncology drug development.