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

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.