Imaging Tumour ATB0,+ Transport Activity by PET with the Cationic Amino Acid O-2((2-[18F]fluoroethyl)methyl-amino)ethyltyrosine

The concentrative amino acid transporter ATB(0,+) (SLC6A14) is under evaluation as a target for anticancer therapy. An ATB(0,+)-selective positron emission tomography (PET) probe could advance preclinical drug development. We characterised the cationic tyrosine analogue O-2((2-[F-18]fluoroethyl)methyl-amino)ethyltyrosine ([F-18]FEMAET) as a PET probe for ATB(0,+) activity. Cell uptake was studied in vitro. ATB(0,+) expression was quantified by real-time PCR. [F-18]FEMAET accumulation in xenografts was investigated by small animal PET with mice. [F-18]FEMAET accumulated in PC-3 and NCI-H69 cancer cells in vitro. As expected for ATB(0,+) transport, uptake was inhibited by LAT/ATB(0,+) inhibitors and dibasic amino acids, and [F-18]FEMAET efflux was only moderately stimulated by extracellular amino acids. ATB(0,+) was expressed in PC-3 and NCI-H69 but not MDA-MB-231 xenografts. PET revealed accumulation in PC-3 and NCI-H69 xenografts and significant reduction by ATB(0,+) inhibition. Uptake was negligible in MDA-MB-231 xenografts. ATB(0,+) activity can be imaged in vivo by PET with [F-18]FEMAET.