Grant: Project Grant

Magnetic resonance imaging (MRI) is an indispensable clinical imaging technique that is used to diagnose a wide range of diseases. More than one-third of MRI exams use an injectable contrast agent to help disease stand out from its healthy surroundings. Current approved contrast agents rely on a metal centre (i.e. gadolinium atom) and, although they are generally considered safe, their long-term safety is of concern. With reduced kidney function, the metal from the contrast agent can accumulate in the body and potentially result in a debilitating disease called 'nephrogenic systemic fibrosis' which has no proven treatment or cure. Moreover, gadolinium accumulates in the normal tissues including the brain even after as few as one injection and the long term effects of this retention are unknown. In order to improve the safety of MRI in general and for kidney disease diagnosis, alternative contrast agents for MRI need to be found. We have developed a new type of contrast agent that does not contain any metal atoms, which would avoid the known and unknown risks of contrast-enhanced MRI for patients with kidney disease. These metal-free contrast agents have already been shown to provide excellent MRI evaluation of kidneys in live mice. Herein we will explore the effect of altering the contrast agent chemistry on its utility for diagnostic imaging. We will focus on developing the best metal-free agent to identify the earliest signs of kidney disease, as well as those that can identify kidney and urinary collecting system cancers with high accuracy. We will also test the safety of these agents relative to current clinical metal-containing MRI contrast agents in order to build support for trialing metal-free contrast agents into humans. The outcome of the current proposal will be the identification and evaluation of a set of contrast agents specifically developed for safer MRI evaluation of the kidney, which is an important clinical need.