Abstract

Motivation: Clinical translation of hyperpolarized 13C-fumarate has the potential to enable early, non-invasive assessment of treatment response in cancer. Goal(s): To advance a novel hyperpolarized probe from the laboratory to the clinic. Approach: Translation involved optimizing clinical scale hyperpolarization, establishing an imaging protocol at clinical field strength (3T), preclinical toxicology and first in-human injections. Results: 13C-fumarate showed good hyperpolarization properties and the imaging protocol achieved sufficient spectral separation of peaks and spatial separation of phantoms respectively. Toxicological assessment demonstrated the safety of 13C-fumarate, no adverse events observed in rodents and humans have so far been observed. Impact: While promising preclinical molecules exist, clinical hyperpolarized 13C MRI lacks probe versatility due to a complex, unclear translation process. This study on fumarate narrows the gap between preclinical and clinical utility and fosters transparent clinical translation pipelines for the field.