mRNA-based MRI contrast agent for precise diagnosis of glioma and pseudoprogression

Precise diagnosis of glioma remains challenging in two aspects: one is to accurately image the tumor margin before surgery, and the other is to distinguish pseudoprogression and true tumor progression after therapy. Here, we developed a non-metallic MRI contrast agent, composed of a serotonin-derived ionizable lipid nanoparticle (LNP) and an mRNA with its 3'UTR engineered for glioma-specific expression. To enhance the contrast signal of the glioma in MRI, the aquaporin-1 (AQP1) mRNA was delivered to encode a water channel on cell membranes. Furthermore, the engineered 3'UTR ensures that the mRNA is degraded in healthy tissues instead of glioma, making pseudoprogression easily detectable by MRI. The mRNA-based contrast agent, named "TARGET", provides an effective complement to gadolinium contrast agents in the diagnosis of brain tumors. This proof-of-concept study demonstrates that TARGET holds promise for substantially enhancing diagnostic accuracy of glioma and pseudoprogression in clinical translation.