Monitoring response to a clinically relevant IDH inhibitor in glioma-Hyperpolarized ¹³C magnetic resonance spectroscopy approaches.

ABSTRACT:

Background

Mutant isocitrate dehydrogenase (IDHmut) catalyzes 2-hydroxyglutarate (2HG) production and is considered a therapeutic target for IDHmut tumors. However, response is mostly associated with inhibition of tumor growth. Response assessment via anatomic imaging is therefore challenging. Our goal was to directly detect IDHmut inhibition using a new hyperpolarized (HP) ¹³C magnetic resonance spectroscopy-based approach to noninvasively assess α-ketoglutarate (αKG) metabolism to 2HG and glutamate.

Methods

We studied IDHmut-expressing normal human astrocyte (NHAIDH1mut) cells and rats with BT257 tumors, and assessed response to the IDHmut inhibitor BAY-1436032 (n ≥ 4). We developed a new ¹³C Echo Planar Spectroscopic Imaging sequence with an o

SUBMITTER: Hong D 

PROVIDER: S-EPMC10681661 | biostudies-literature | 2023 Jan-Dec

REPOSITORIES: biostudies-literature