Inflammatory microenvironment-responsive MR imaging contrast agents

Abstract

Inflammation is a hallmark of numerous acute and chronic diseases, presenting a unique opportunity for molecular imaging. Magnetic resonance imaging, while widely used for its excellent spatial resolution and soft tissue contrast, traditionally lacks the sensitivity and specificity needed to monitor dynamic biochemical processes. To address this gap, a new class of activatable MR imaging contrast agents has emerged - designed to respond selectively to inflammatory triggers such as acidic pH, reactive oxygen species, and proteolytic enzyme activity. This review highlights recent advances in the development of such smart contrast agents, emphasizing their molecular design, activation mechanisms, and preclinical validation. By enabling localized signal enhancement in response to inflammation, these agents offer the potential to improve diagnostic accuracy, stratify disease severity, and monitor therapeutic response with high spatial and temporal resolution. The translation of these agents into clinical practice will depend on continued optimization of stability, safety, and imaging performance across diverse disease models. We performed a literature search using PubMed and Google Scholar for articles published between January 2000 and February 2025 on activatable MR imaging contrast agents, redox-responsive nanoparticles, and imaging of inflammatory processes.

Keywords: Activatable MR contrast agents; enzymes; inflammation; pH; reactive oxygen species.