Biological evaluation of 3-[F]fluoro--methyl-D-tyrosine (D-[F]FAMT) as a novel amino acid tracer for positron emission tomography

Ohshima, Yasuhiro; Hanaoka, Hirofumi*; Tominaga, Hideyuki*; Kanai, Yoshikatsu*; Kaira, Kyoichi*; Yamaguchi, Aiko*; Nagamori, Shushi*; Oriuchi, Noboru*; Tsushima, Yoshito*; Endo, Keigo*; Ishioka, Noriko

3-[F]Fluoro--methyl-L-tyrosine (L-[F]FAMT) is a useful amino acid tracer, and it is selectively accumulated in the tumor without an incorporation in the protein synthesis. However, L-[F]FAMT is highly retained in the kidney, which causes the reduction of sensitivity for tumor detection by positron emission tomography (PET). L-amino acids have corresponding D-isomers which have some favorable properties for development of PET tracers. Since mammals rarely use D-amino acids for their biological activity, D-amino acids would not be taken up by the normal tissues. In addition, D-amino acids are highly excreted in the urine compared with L-isomers, and rapidly cleared from the circulation. Thus, D-isomer of FAMT would lower the high retention of L-isomer in the kidney and allow clear imaging of the tumor by PET. In this study, we synthesized 3-[F]fluoro--methyl-D-tyrosine (D-[F]FAMT) and evaluated its potential. In biodistribution studies, D-[F]FAMT showed rapid clearance from blood, marked accumulation and retention in the tumor and low retention in non-target organs, especially kidney. Furthermore, PET imaging using D-[F]FAMT enabled clear visualization of implanted tumor, compared with L-[F]FAMT. In conclusion, D-[F]FAMT could potentially serve as a useful tracer for imaging malignant tumors.