Hepatic organic anion transporting polypeptides (OATPs) as MRI reporter proteins

Organic anion transporting polypeptides (OATPs) are hepatic membrane transporters responsible for the uptake of numerous endogenous compounds and drugs. Among these, OATP1B1 and OATP1B3 in humans, and their orthologs in other species, mediate the cellular uptake of clinically approved hepatospecific MRI contrast agents, rendering them suitable candidates for use as MRI reporter proteins. This review examines the structural biology, evolutionary divergence, and transport mechanisms of hepatic OATPs, with a focus on their capacity to serve as genetically encoded imaging reporters. We survey the uptake and imaging characteristics of clinically available and experimental contrast agents in species-specific contexts and detail how hepatic OATPs have been leveraged in preclinical models for tracking engineered cells in oncology, regenerative medicine, and immunotherapy. Special attention is given to the pioneering studies that established OATP1A1 and OATP1B3 as MRI reporter proteins, the challenges related to contrast dose and imaging timing, and the emerging solutions such as dual-reporter systems and dynamic imaging protocols. Compared to traditional labeling strategies like iron oxide nanoparticles, OATP-based reporters enable positive contrast on T1-weighted MRI, avoid signal ambiguity, and permit multimodal imaging using clinically approved probes. The integration of hepatic OATPs as MRI reporter proteins offers a translationally feasible platform for non-invasive, longitudinal imaging of therapeutic cells in clinical trials and medicine. This technology has the potential to improve safety, efficacy, and mechanistic understanding across a wide array of biomedical applications.