Amino acid transporter expression and 18F-FACBC uptake at PET in primary prostate cancer

Little is known about the transport mechanism of anti-3-18F-fluorocyclobutane-1-carboxylic acid (FACBC) into prostate tumors. Because of the structural similarity to natural amino acids, FACBC is anticipated to cross the cell membrane via amino acid transporters, and preclinical studies have suggested that ASCT2, LAT1 and SNAT2 are involved. In 16 patients with intermediate or high-risk prostate cancer we matched the FACBC uptake from clinical PET to the location of punch biopsies from resected prostatectomy specimens and compared maximum standardized uptake value (SUVmax) with the gene expression of 40 amino acid transporters. The study also included immunohistochemistry for the three amino acid transporters ASCT2, LAT1 and SNAT2. Furthermore, we performed global gene expression analysis of the biopsies to investigate biological processes associated with FACBC uptake. Several amino acid transporters had a higher gene expression level than the others, but we found no significant correlations between SUVmax and the gene expression levels of any of 40 different amino acid transporters. In the immunohistochemical analyses, ASCT2 and SNAT2 were highly expressed, but not correlated to SUVmax. LAT1 had low gene- and protein expression. Global gene expression analyses identified 153 unique genes that were positively correlated to SUVmax. These genes were found to be associated with gene sets reflecting intracellular transport and high metabolic activity. Based on the study findings we propose that the uptake mechanism of FACBC is more complex than mediated by a few amino acid transporters.