Manganese-bound Protein-based Hydrogel as a T1-brightening Theranostic Agent

Motivation: Safety concerns with gadolinium(Gd)-based MRI agents have spurred interest in safer alternatives. Manganese(Mn), with strong T1-brightening potential, offers a promising but underexplored option for MRI that become increasingly advantageous combined with hydrogels for sustained release. Goal(s): This study aims to develop a hybrid Mn-bound protein-hydrogel Q5•Mn, providing a safer and customizable alternative to Gd with adjustable Mn-binding, relaxivity, and imaging stability. Approach: Using computational design, we engineered Q5•Mn for optimal T1-brightening and material strength. Results: In-vitro and in-vivo studies of Q5•Mn hydrogels demonstrated strong Mn-binding, robust T1-weighted contrast, gelation stability, and improved signal retention, establishing them as a safe, effective MRI contrast option. Impact: The Mn-bound protein-hydrogel, Q5•Mn, provides a safer, tunable MRI contrast agent with prolonged T1-brightening stability, offering a viable alternative to gadolinium. This innovation supports safer, targeted imaging in clinical settings and opens new possibilities for protein-based theranostic agents in MRI.