Metal‐Based Nanoparticle Magnetic Resonance Imaging Contrast Agents: Classifications, Issues, and Countermeasures toward their Clinical Translation

Abstract Metal‐based nanoparticles, especially gadolinium, manganese, and iron, have gained ground in the research of magnetic resonance imaging (MRI) contrast agents. Over the years, contrast agents based on these paramagnetic and superparamagnetic nanomaterials have merited keen attention in the biomedical field due to their desired properties such as sizeable magnetic susceptibility, tunable size, easy surface functionalization, low toxicity, etc. Gadolinium‐based chelates are the traditional MRI contrast agents in the clinic but require improved relaxivities and pharmacokinetics. Nanoparticles possess a larger surface area, demonstrate a longer retention time in the body, and allow the conjugation of several functional molecules to enhance tumor targeting, making them more advantageous. The pursuit of clinically acceptable MRI contrast agents has generated diverse nanoparticles which have augmented their properties, performance, and relevance. Yet, most nanoparticles have not headed for the clinic for various reasons. Here, metal‐based MRI contrast agents and their contrast mechanisms are briefly described. According to relaxation times, T 1 and T 2 , the different types that have evolved are reviewed, emphasizing the properties that have improved their function as MRI contrast agents. Finally, pertinent issues restraining their clinical translation and potential measures to develop more effective and clinically relevant MRI contrast agents are discussed.