Chemical design of nanoprobes for T1-weighted magnetic resonance imaging

Magnetic resonance imaging (MRI), which offers a number of advantages such as unlimited tissue penetration, zero ionizing radiation, and a noninvasive nature, has received considerable attention over the past two decades as a technique for clinical diagnosis. To improve imaging sensitivity, contrast agents have been employed to accelerate the relaxation rate of water molecules and thus to increase the contrast between specific tissues or organs of interest. However, conventional contrast agents such as Gd3+-based T-1 complexes and iron oxide nanoparticle-based T-2 contrast agents have been proven to have adverse effects. The former may cause fatal nephrogenic systemic fibrosis (NSF) and difficulty in metabolism, while the latter is less sensitive due to the background interference. Also, their development has been well documented. Therefore, the orientation of this review will be geared toward the newly developed nanoparticulate agents that serve as better alternatives. In this regard, the recent advances on various nanostructured Mn/Fe-based T-1 contrast agents seem to fit these categories. As they reveal longer circulation half-life and better biocompatibility, they have demonstrated themselves as a promising T-1 candidate for MRI. The focus of this review will be on the preparation and fabrication of T-1 contrast agents that contain mainly paramagnetic manganese and iron ions, with special attention being paid to the growth mechanism. Additional emphasis is also put on their progressive development in an aim to overcome the drawbacks of classical iron oxide nanoparticle-based T-2 and Gd3+-based T-1 contrast agents. Representative applications in vitro and in vivo will be presented for this new generation of contrast agents. The pros and cons of each case are also briefly summarized.