Mass spectrometry imaging of L-[ring-13C6]-labeled phenylalanine and tyrosine kinetics in non-small cell lung carcinoma

Abstract

Background

Metabolic reprogramming is a common phenomenon in tumorigenesis and tumor progression. Amino acids are important mediators in cancer metabolism, and their kinetics in tumor tissue are far from being understood completely. Mass spectrometry imaging is capable to spatiotemporally trace important endogenous metabolites in biological tissue specimens. In this research, we studied L-[ring-¹³C₆]-labeled phenylalanine and tyrosine kinetics in a human non-small cell lung carcinoma (NSCLC) xenografted mouse model using matrix-assisted laser desorption/ionization Fourier-transform ion cyclotron resonance mass spectrometry imaging (MALDI-FTICR-MSI).

Methods

We investigated the L-[ring-¹³C₆]-Phenylalanine (¹³C₆-Phe) and L-[ring-¹³C₆]-Tyrosine (¹³C₆-Tyr) kinetics at 10 min (n = 4), 30 min (n = 3), and 60 min (n = 4) after tracer injection and sham-treated group (n = 3) at 10 min in mouse-xenograft lung tumor tissues by MALDI-FTICR-MSI.

Results

The dynamic changes in the spatial distributions of 19 out of 20 standard amino acids are observed in the tumor tissue. The highest abundance of ¹³C₆-Phe was detected in tumor tissue at 10 min after tracer injection and decreased progressively over time. The overall enrichment of ¹³C₆-Tyr showed a delayed temporal trend compared to ¹³C₆-Phe in tumor caused by the Phe-to-Tyr conversion process. Specifically, ¹³C₆-Phe and ¹³C₆-Tyr showed higher abundances in viable tumor regions compared to non-viable regions.

Conclusions

We demonstrated the spatiotemporal intra-tumoral distribution of the essential aromatic amino acid ¹³C₆-Phe and its de-novo synthesized metabolite ¹³C₆-Tyr by MALDI-FTICR-MSI. Our results explore for the first time local phenylalanine metabolism in the context of cancer tissue morphology. This opens a new way to understand amino acid metabolism within the tumor and its microenvironment.