A New Type of Gadodiamide-Conjugated Chitosan Amphiphiles For MR Imaging: Molecular Structural Analysis and Animal Imaging
Cancer has been the leading cause of death over decades worldwide, one of the main reasons is its difficulty of tumor detection in early stage, and has long been a prime research objective in the field from materials science to nanomedicine. In clinical practices, magnetic resonance imaging (MRI), which uses non-ionizing radiation, is a non-invasive and powerful diagnostic tool for cancer detection. MRI often uses contrast agent to make the images of human body clear. The current commonly used contrast agent is gadolinium(64Gd)-based contrast agent (GBCA), which is a coordination complex and its coordination center is Gd3+. It is important to note that de-chelated Gd3+ ions are toxic to the human body. More data show that if GBCA is used in patients with poor renal function, it will lead to an adverse effect, nephrogenic systemic fibrosis. To improve the biosafety of GBCA, we have combined amphiphilic chitosan, which is a highly biocompatible polymer developed in our lab, and gadodiamide, the contrast agent frequently used in clinics, through condensation reaction and become novel macromolecular MRI contrast agent. The most important advantages for this newly-synthesized macromolecular MRI contrast agent are higher contrast enhancement and lower dose than the native Gadodiamide used. Through the results of MRI, injection of the macromolecular MRI contrast agent in the tail vein of mice clearly demonstrated that the contrast enhancement of the kidney was much higher than that of gadodiamide. Additionally, the experimental results showed excellent active targeting contrast image toward xenograft tumor in-vivo, suggesting a potential development in clinical translation for tumor diagnosis.