Hyperpolarised MR technologies and molecular probes as alternatives for conventional metal-containing contrast agents for MRI examinations

Recently, the European Medicines Agency (EMA) and the U.S. Food & Drug Administration (FDA) recommended suspension and warning labels for Gadolinium (Gd)-bearing CAs (GBCA) used in magnetic resonance imaging (MRI). This decision, although made in the absence of any clinical evidence, relates to potential major health concerns resulting from long-term accumulation of Gd containing species in patients’ bodies. This sends a clear message that we need to carefully consider the necessity of each contrast injection in individuals undergoing an MRI scan. However, for a number of diagnostic procedures, such as tumour characterisation, the use of a CA is often essential. The accumulation of Gd in different organs (including the brain) and GBCA-related diseases requires the scientific community to seek radically new alternatives. The AlternativesToGd vision is to identify and validate radically new compounds and technologies as alternatives to GBCAs. The new compounds and technologies developed in this proposal will be tested in animal models of disease and the most promising ones selected for further clinical development. The expected outcomes should radically impact the field, likely leading to a paradigm shift in MR-based diagnosis and thus being highly beneficial to society. The AlternativesToGd consortium will develop a new class of MRI CAs that will be metal-free, safe, and completely eliminated from the human body after the MRI exam. The agents will consist of small endogenous molecules, in which nuclear spins will be hyperpolarised to ensure high sensitivity to MR detection, even at very low doses. A major challenge and risk arises from the rapid decay of the hyperpolarised (HP) state. As enabling technologies, AlternativesToGd focuses on three leading and innovative hyperpolarisation techniques and on unique agents showing HP state lifetimes that are sufficiently long to enable diagnostic contrast-enhanced MRI approaches with so far unobtained sensitivity.