Abstract <p> <?tk 2?>Sepsis-induced acute kidney injury (AKI) is a critical condition characterized by high mortality and limited early diagnostic tools. This study presents the development of a novel multimodal nanoprobe, ⁶⁸Ga/99mTc@LTH-SPIONs, for targeted detection and monitoring of sepsis-induced AKI. By combining PET/SPECT imaging capabilities of radiolabeled isotopes (⁶⁸Ga and 99mTc) with the anatomical resolution of superparamagnetic iron oxide nanoparticles (SPIONs) for MRI, the nanoprobe facilitates precise and non-invasive imaging. Surface modification with the LTH peptide, which specifically targets Kidney Injury Molecule-1 (Kim-1), enhances the nanoprobe’s diagnostic specificity. Extensive in vitro and in vivo evaluations revealed low cytotoxicity, excellent biocompatibility, and effective renal targeting, with metabolites predominantly cleared through urine. In a sepsis AKI mouse model, the nanoprobe provided sensitive and specific imaging, enabling early detection of kidney injury. This study underscores the potential of Kim-1-targeted nanoprobes as a powerful tool for elucidating cellular injury mechanisms and monitoring therapeutic interventions in AKI.</p> Graphical abstract <p></p>