Advances in redox imaging for cancer diagnosis and therapy.

Abstract

Cancer remains a leading cause of global morbidity and mortality, necessitating continuous innovations in diagnosis and therapy. Redox biology, the balance between reactive oxygen species production and antioxidant defenses, plays a central role in tumor initiation, progression, and therapeutic response. Elevated reactive oxygen species levels drive DNA damage, genomic instability, and tumor-promoting signaling, whereas adaptive antioxidant responses promote survival, therapeutic resistance, and recurrence. Chemotherapy and radiotherapy partly exert their cytotoxic effects through reactive oxygen species generation. However, tumors with enhanced redox-buffering capacity often evade reactive oxygen species-mediated killing. Ferroptosis, iron-dependent cell death driven by lipid peroxidation, is a key redox-linked pathway that synergizes with radiotherapy, offering new radiosensitization strategies. Redox imaging is a non-invasive approach to map oxidative and reductive dynamics in tumors. This review outlines the unique strengths of advancements, including optical imaging with redox-sensitive probes, positron emission tomography tracers targeting glutamine metabolism or system X_c ^-, magnetic resonance imaging with nitroxide-based probes and dynamic nuclear polarization, and electron paramagnetic resonance imaging. Together, these developments underscore the potential of redox imaging as a research and clinical tool. By enabling functional tumor characterization, patient stratification, and treatment monitoring, redox-based imaging provides a framework for precision oncology and development of redox-modulating therapies.