Metabolic detection of BTK inhibition in mantle cell lymphoma models

Motivation: The current approaches to assess Bruton’s kinase inhibitor (BTK) therapeutic effects in cancer are not ideal. Goal(s): Employing metabolic imaging, we evaluated the mode of action of ibrutinib (IBR), a BTK inhibitor, in mantle cell lymphoma (MCL) cells and xenografts. Approach: Our approach using 1H MRS demonstrated that, in sensitive MCL models, IBR significantly impacted critical metabolic pathways, including glycolysis, glutaminolysis, and phospholipid metabolism, but had far less of an impact on IBR-poorly responsive cells. Results: Changes in 1H MRS detectable lactate, alanine, and choline concentrations on various MCL models emerged as promising biomarkers of response or resistance to IBR. Impact: Decreased intra-tumoral concentrations of lactate, alanine, and choline measured by 1H MRS during treatment can potentially become early and sensitive biomarkers of BTK inhibition in MCL and, likely, other lymphoma treatments.