MRI of ASCT2-mediated amino acid uptake in xenograft tumor models

We investigated alanine as a magnetic resonance imaging (MRI) biomarker for alanine-serine-cysteine transporter 2 (ASCT2), the primary transporter for glutamine in cancer. Alanine exhibited higher contrast using the chemical exchange saturation transfer (CEST) method than other major ASCT2 substrates. Upon bolus injection of alanine (6 mmole/kg), CEST MRI enhancement in vivo was higher in SLC1A5-overexpressing Pa20c pancreatic tumors than naïve tumors (p < 0.0001). Enhancement was more pronounced in LNCaP prostate tumors than DU-145 prostate tumors in vivo (p < 0.0001). The temporal dynamics of alanine-weighted CEST (ALAwCEST) signal enhancement depended on the volume of the tumor, which histological analysis revealed to be due to alterations in the expression and distribution of ASCT2 and CD31-positive blood vessels. Mass spectrometric imaging of ¹³C-labeled metabolites confirmed differences in alanine uptake and metabolism in prostate tumors. We demonstrated the feasibility of ALAwCEST imaging for reporting ASCT2-mediated uptake in multiple human cancer models.