Synthesis and preliminary biological evaluation of O-2((2-[18F]fluoroethyl)methylamino)ethyltyrosine ([18F]FEMAET) as a potential cationic amino acid PET tracer for tumor imaging

Amino acid transport is an attractive target for oncologic imaging. Despite a high demand of cancer cells for cationic amino acids, their potential as PET probes remains unexplored. Arginine, in particular, is involved in a number of biosynthetic pathways that significantly influence carcinogenesis and tumor biology. Cationic amino acids are transported by several cationic transport systems including, ATB0,+ (SLC6A14), which is upregulated in certain human cancers including cervical, colorectal and estrogen receptor-positive breast cancer. In this work, we report the synthesis and preliminary biological evaluation of a new cationic analog of the clinically used PET tumor imaging agent O-(2-[18F]fluroethyl)-l-tyrosine ([18F]FET), namely O-2((2-[18F]fluoroethyl)methylamino)ethyltyrosine ([18F]FEMAET). Reference compound and precursor were prepared by multi-step approaches. Radiosynthesis was achieved by no-carrier-added nucleophilic [18F]fluorination in 16–20 % decay-corrected yields with radiochemical purity >99 %. The new tracer showed good stability in vitro and in vivo. Cell uptake assays demonstrated that FEMAET and [18F]FEMAET accumulate in prostate cancer (PC-3) and small cell lung cancer cells (NCI-H69), with an energy-dependent mechanism. Small animal PET imaging with NCI-H69 xenograft-bearing mice revealed good tumor visualization comparable to [18F]FET and low brain uptake, indicating negligible transport across the blood–brain barrier. In conclusion, the non-natural cationic amino acid PET probe [18F]FEMAET accumulates in cancer cells in vitro and in vivo with possible involvement of ATB0,+.