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

Abstract

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(0,+) (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-[(18)F]fluroethyl)-L-tyrosine ([(18)F]FET), namely O-2((2-[(18)F]fluoroethyl)methylamino)ethyltyrosine ([(18)F]FEMAET). Reference compound and precursor were prepared by multi-step approaches. Radiosynthesis was achieved by no-carrier-added nucleophilic [(18)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 [(18)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 [(18)F]FET and low brain uptake, indicating negligible transport across the blood-brain barrier. In conclusion, the non-natural cationic amino acid PET probe [(18)F]FEMAET accumulates in cancer cells in vitro and in vivo with possible involvement of ATB(0,+).

• Authors: Aristeidis Chiotellis, Adrienne Müller, Karin Weyermann, Dominique S Leutwiler, Roger Schibli, Simon M Ametamey, Stefanie D Krämer, Linjing Mu
• Journal: Amino acids (Amino Acids) Vol. 46 Issue 8 Pg. 1947-59 (Aug 2014) ISSN: 1438-2199 [Electronic] Austria
• PMID: 24802247 (Publication Type: Journal Article)

Chemical References

• Amino Acid Transport Systems
• Amino Acids
• Fluorine Radioisotopes
• O-2((2-fluoroethyl)methylamino)ethyltyrosine
• Radiopharmaceuticals
• Tyrosine

Topics

• Amino Acid Transport Systems (analysis)
• Amino Acids (analysis, metabolism)
• Animals
• Blood-Brain Barrier
• Cell Line, Tumor
• Diagnostic Imaging (methods)
• Female
• Fluorine Radioisotopes (chemistry)
• Humans
• Lung Neoplasms (diagnosis, diagnostic imaging)
• Male
• Mice
• Mice, Nude
• Neoplasm Transplantation
• Positron-Emission Tomography (methods)
• Prostatic Neoplasms (diagnosis, diagnostic imaging)
• Protein Transport
• Radiopharmaceuticals
• Small Cell Lung Carcinoma (diagnosis, diagnostic imaging)
• Transplantation, Heterologous
• Tyrosine (analogs & derivatives, chemical synthesis)