Synthesis and preliminary biological evaluation of O-2((2-[F]fluoroethyl)methylamino)ethyltyrosine ([F]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, ATB (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-[F]fluroethyl)- l-tyrosine ([F]FET), namely O-2((2-[F]fluoroethyl)methylamino)ethyltyrosine ([F]FEMAET). Reference compound and precursor were prepared by multi-step approaches. Radiosynthesis was achieved by no-carrier-added nucleophilic [F]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 [F]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 [F]FET and low brain uptake, indicating negligible transport across the blood-brain barrier. In conclusion, the non-natural cationic amino acid PET probe [F]FEMAET accumulates in cancer cells in vitro and in vivo with possible involvement of ATB. [ABSTRACT FROM AUTHOR]