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Abstract #0225

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

Jacob Chen Ming Low1, Jianbo Cao1, Friederike Hesse1, Alan Wright1, and Kevin Brindle1
1Cancer Research UK, Cambridge Institute, Cambridge, United Kingdom

Synopsis

Keywords: Tumors (Post-Treatment), Deuterium

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.

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