Relaxivity Optimization of a PEGylated Iron-Oxide-Based Negative Magnetic Resonance Contrast Agent for T₂-Weighted Spin–Echo Imaging

Concerning the outer sphere relaxation theory, the sensitivity of a T(2) MRI contrast agent, expressed by the transverse relaxivity r(2), depends on the diffusion length of water molecules relative to the particle size. For T(2)-weighted spin-echo imaging, theoretical concepts reveal three regimes regarding the r(2) relaxivity depending on the nanocrystal size: the motional averaging regime (MAR), the static dephasing regime (SDR), and the echo-limiting regime (ELR). The r(2) maximum corresponds to the SDR, which represents a small size regime. To verify the theoretical concepts and to adjust the SDR, tailor-made T(2) contrast agents were synthesized by controlled self-assembly of superparamagnetic iron oxide nanocrystals (SPIOs) into raspberry-like nanoclusters with diameters of 30-200 nm using a PEG-based ligand. The results highlight an opportunity to optimize the relaxivity of T(2) contrast agents by tuning the cluster size of SPIO nanocrystals.