Current Status and Future Aspects of Gadolinium Oxide Nanoparticles as Positive Magnetic Resonance Imaging Contrast Agents

Although numerous studies have investigated gadolinium oxide (Gd₂O₃) nanoparticles (NPs) as positive (T₁) magnetic resonance imaging (MRI) contrast agents (CAs), comprehensive reviews on this topic remain scarce. Therefore, it is essential to evaluate their current status and outline prospects. Despite promising physicochemical properties such as considerably higher relaxivities compared to 3–5 s⁻¹mM⁻¹ of clinically approved Gd(III)-chelate contrast agents and encouraging results from in vivo animal studies such as highly improved contrast enhancements, drug loading, and tumor targeting, extensive in vivo toxicity assessments including long-term toxicity and formulation advancements suitable for renal excretion (d < ~3 nm) are still required for clinical translation. This review summarizes the synthesis, characterization, in vitro and in vivo toxicity, and in vivo MRI applications of surface-modified Gd₂O₃ NPs as T₁ MRI CAs. Finally, future perspectives on the development of surface-modified Gd₂O₃ NPs as potential next-generation T₁ MRI CAs are discussed.