Feasibility of 7-T fluorine magnetic resonance spectroscopic imaging ((19)F MRSI) for TAS-102 metabolite detection in the liver of patients with metastatic colorectal cancer

Trifluridine/tipiracil (TAS-102) has shown a significant overall survival benefit in patients with heavily pre-treated metastatic colorectal cancer. However, predicting treatment response and toxicity in individual patients remains challenging. Fluorine ((19)F)-containing drugs can be detected with magnetic resonance spectroscopy (MRS) to determine the metabolic rates and the biodistribution of the drug in normal and tumour tissue, which are related to treatment efficacy and toxicity. This is the first study to investigate the potential of 7-T (19)F-MRS to detect TAS-102 metabolites in humans. We demonstrate that, with the used setup, TAS-102 is not detectable in liver metastases of metastatic colorectal cancer patients on a normal treatment schedule. Therefore, (19)F-MRS TAS-102 metabolite detection is not yet useful for the clinical early prediction of treatment response. As (19)F-MRS is able to detect TAS-102 in phantom and murine models, the use of (19)F-MRS remains a potential tool to noninvasively detect and possibly monitor the metabolism when higher dosages of TAS-102 are administered, for example in organoid and animal studies.