Deuterium metabolic imaging detects early treatment response to mitochondrial complex 1 inhibition

Motivation: The oxidative subtype of glioblastoma (GB) has potential mitochondrial therapeutic vulnerabilities that can be targeted for treatment. Goal(s): To detect early response to a mitochondrial complex 1 inhibitor, IACS-010759, using deuterium metabolic imaging (DMI). Approach: Measurements of oxygen consumption, extracellular acidification rate and 2H-labelled lactate production in GB cell suspensions in vitro and 2H-labelled lactate and Glx production from [6,6’-2H2]glucose in GB xenografts in vivo, pre- and post-treatment. Results: DMI detects an in vivo response to treatment with IACS-010759 from measurements of decreased 2H-labeled Glx production and increased 2H-labeled lactate production. Impact: Deuterium metabolic imaging can be used to detect the early response of a glioblastoma model to treatment with a mitochondrial complex 1 inhibitor.