Hyperpolarized 13C-Pyruvate to Assess Response to Anti-PD1 Immune Checkpoint Inhibition in YUMMER 1.7 Melanoma Xenografts

Abstract

There is currently no consensus to determine which advanced melanoma patients will benefit from immunotherapy, highlighting the critical need to identify early-response biomarkers to immune checkpoint inhibitors. The aim of this work was to evaluate in vivo metabolic spectroscopy using hyperpolarized (HP) 13C-pyruvate and 13C-glucose to assess early response to anti-PD1 therapy in the YUMMER1.7 syngeneic melanoma model. The xenografts showed a significant tumor growth delay when treated with two cycles of an anti-PD1 antibody compared to an isotype control antibody. 13C-MRS was performed in vivo after the injection of hyperpolarized 13C-pyruvate, at baseline and after one cycle of immunotherapy, to evaluate early dynamic changes in 13C-pyruvate–13C-lactate exchange. Furthermore, ex vivo 13C-MRS metabolic tracing experiments were performed after U-13C-glucose injection following one cycle of immunotherapy. A significant decrease in the ratio of HP 13C-lactate to 13C-pyruvate was observed in vivo in comparison with the isotype control group, while there was a lack of change in the levels of 13C lactate and 13C alanine issued from 13C glucose infusion, following ex vivo assessment on resected tumors. Thus, these results suggest that hyperpolarized 13C-pyruvate could be used to assess early response to immune checkpoint inhibitors in melanoma patients.