Metabolic imaging using hyperpolarized ¹³ C-pyruvate to assess sensitivity to the B-Raf inhibitor vemurafenib in melanoma cells and xenografts.

ABSTRACT: Nearly all melanoma patients with a BRAF-activating mutation will develop resistance after an initial clinical benefit from BRAF inhibition (BRAFi). The aim of this work is to evaluate whether metabolic imaging using hyperpolarized (HP) ¹³ C pyruvate can serve as a metabolic marker of early response to BRAFi in melanoma, by exploiting the metabolic effects of BRAFi. Mice bearing human melanoma xenografts were treated with the BRAFi vemurafenib or vehicle. In vivo HP ¹³ C magnetic resonance spectroscopy was performed at baseline and 24 hours after treatment to evaluate changes in pyruvate-to-lactate conversion. Oxygen partial pressure was measured via electron paramagnetic resonance oximetry. Ex vivo qRT-PCR, immunohistochemistry and WB analysis were performed on tumou

SUBMITTER: Acciardo S 

PROVIDER: S-EPMC6991684 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature