Rational Design of Magnetic Nanoparticles as T₁-T₂ Dual-Mode MRI Contrast Agents

Magnetic nanoparticles (MNPs), either paramagnetic or superparamagnetic depending on their composition and size, have been thoroughly studied as magnetic resonance imaging (MRI) contrast agents using in vitro and in vivo biomedical preclinical studies, while some are clinically used. Their magnetic properties responsible in some cases for high magnetization values, together with large surface area-to-volume ratios and the possibility of surface functionalization, have been used in MRI-based diagnostic and theranostics applications. MNPs are usually used as positive (T₁) or negative (T₂) MRI contrast agents, causing brightening or darkening of selected regions in MRI images, respectively. This review focusses on recent developments and optimization of MNPs containing Gd, Mn, Fe and other lanthanide ions which may function as dual-mode T₁-T₂ MRI contrast agents (DMCAs). They induce positive or negative contrast in the same MRI scanner upon changing its operational mode between T₁-weighted and T₂-weighted pulse sequences. The type of contrast they induce depends critically on their r₂/r₁ relaxivity ratio, which for DMCAs should be in the 2-10 range of values. After briefly discussing the basic principles of paramagnetic relaxation in MNPs, in this review, the basic strategies for the rational design of DMCAs are presented and typical examples are discussed, including in vivo preclinical applications: (1) the use of NPs with a single type of contrast material, Gd- or Mn-based NPs or superparamagnetic NPs with appropriate size and magnetization to provide T₂ and T₁ contrast; and (2) inclusion of both types of T₁ and T₂ contrast materials in the same nanoplatform by changing their relative positions.