SingMet · Development of MRI contrast agents based on long-lived singlet states

Development of MRI contrast agents based on long-lived singlet states

Cancer is one of the leading causes for death accounting to 8.8 million in 2015 (http://www.who.int/mediacentre/factsheets/fs297/en/). It is predicted that the number of yearly cancer cases increases from 14 million to about 24 million over the next two decades. For developing cures new investigation possibilities and improved diagnostics at an early stage are necessary. Magnetic resonance imaging (MRI) is an excellent method for the detection of diseases. Its advantage is a spatial resolution down to tens of micrometer, good contrast in soft tissue and the possibility to investigate dynamics. The main drawback of MRI is the low sensitivity, limiting the resolution, detectable amounts of metabolites and tumor tissue. To overcome sensitivity problems contrast agents are being developed that are mainly based on gadolinium complexes and iron oxide for in vivo human use. Although these contrast agents have found broad applications, limitations exist: Gadolinium contrast agents need to accumulate in high concentrations (millimolar) in tissue which is not always feasible and iron oxide is often accumulated in the liver due to unfavourable pharmacokinetics. In this project the goal is to develop contrast agents for MRI utilizing the concepts of hyperpolarization and singlet state nuclear magnetic resonance (NMR). Hyperpolarization enhances detectable NMR signals by over four orders of magnitude and singlet states can be utilized to conserve the hyperpolarization in NMR "silent" states. The enhanced signal can be read out at a later stage of time either by chemically breaking the molecules symmetry or by applying radiofrequency pulses. Thus, it becomes possible to detect NMR signals after minutes instead of seconds compared to state-of-the-art metabolic tracers. Moreover, this technique leads to nanomolar limits of detection, which is several orders of magnitude higher than conventional contrast agents. Chemical transformations that break the chemical symmetry and make stored hyperpolarization detectable may be due to enzymes in organisms and can be used as diagnostics for cancer cells. The overarching goal of the project is to develop new molecules that have potential to act as MRI contrast agents without the use of ionizing radiation (such as in positron emission tomography) or heavy metals with toxicity concerns. This will be achieved with hyperpolarized tracers with nanomolar detection limits upon hyperpolarization that undergo chemical transformation induced by enzymes.

Data: CORDIS, © European Union