title: Biological evaluation of 3-[(18)F]fluoro-α-methyl-D-tyrosine (D-[(18)F]FAMT) as a novel amino acid tracer for positron emission tomography.
abstract: OBJECTIVE
  3-[(18)F]Fluoro-α-methyl-L-tyrosine (L-[(18)F]FAMT) is a useful amino acid tracer for positron emission tomography (PET) imaging of malignant tumors. Because D-amino acids are not well distributed in non-target organs and are rapidly excreted in urine, the D-isomer of [(18)F]FAMT could allow clear PET imaging of tumors early after administration. In this study, we prepared 3-[(18)F]fluoro-α-methyl-D-tyrosine (D-[(18)F]FAMT) and evaluated its usefulness.
  
  
  METHODS
  D-[(18)F]FAMT was synthesized according to the method for preparation of L-[(18)F]FAMT. The in vitro and in vivo stability of [(18)F]FAMT were evaluated by high-performance liquid chromatography. Cellular uptake of [(18)F]FAMT was evaluated using LS180 colon adenocarcinoma cells. Biodistribution studies were performed in LS180 tumor-bearing mice, and the tumors were imaged using a small-animal PET scanner.
  
  
  RESULTS
  The radiolabeling yield of D-[(18)F]FAMT was approximately 10 %, similar to that of L-[(18)F]FAMT. Over 95 % of D-[(18)F]FAMT remained intact in mice until 60 min after administration. D-[(18)F]FAMT was gradually taken up by the LS180 cells. Tumor uptake of D-[(18)F]FAMT was competitively inhibited by pretreatment with α-methyl-L-tyrosine, a selective substrate for the system L-amino acid transporter 1 (LAT1), suggesting the involvement of LAT1 in tumor uptake of D-[(18)F]FAMT. In biodistribution studies, D-[(18)F]FAMT showed rapid clearance from the blood, marked accumulation and retention in the tumor, and lower accumulation in non-target organs, especially kidney and pancreas, compared to L-[(18)F]FAMT. The amount of D-[(18)F]FAMT in the tumor was also reduced, and tumor-to-blood ratio and tumor-to-muscle ratio of D-[(18)F]FAMT were similar to those of L-[(18)F]FAMT at every time point. PET imaging with D-[(18)F]FAMT did not provide a clear image of the tumor early after administration. However, D-[(18)F]FAMT provided higher tumor-to-background contrast than L-[(18)F]FAMT.
  
  
  CONCLUSIONS
  D-[(18)F]FAMT showed rapid blood clearance, low accumulation in non-target organs, and tumor-selective imaging compared with L-[(18)F]FAMT. Thus, D-[(18)F]FAMT could potentially serve as a novel PET tracer for imaging malignant tumors.
authors: Medical Radioisotope Application Group, Quantum Beam Science Directorate, Japan Atomic Energy Agency, 1233 Watanuki, Takasaki, Gunma, 370-1292, Japan. ohshima.yasuhiro@jaea.go.jp
authors: Yasuhiro
authors: Y
authors: Ohshima
authors: Hirofumi
authors: H
authors: Hanaoka
authors: Hideyuki
authors: H
authors: Tominaga
authors: Yoshikatsu
authors: Y
authors: Kanai
authors: Kyoichi
authors: K
authors: Kaira
authors: Aiko
authors: A
authors: Yamaguchi
authors: Shushi
authors: S
authors: Nagamori
authors: Noboru
authors: N
authors: Oriuchi
authors: Yoshito
authors: Y
authors: Tsushima
authors: Keigo
authors: K
authors: Endo
authors: Noriko S
authors: NS
authors: Ishioka
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D004355:Drug Stability; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics*; D006801:Humans; D008657:Metabolic Clearance Rate; D008781:Methyltyrosines / Q000493:pharmacokinetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009928:Organ Specificity; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution
chemical_list: C105991:3-fluoro-alpha-methyltyrosine; D005462:Fluorine Radioisotopes; D008781:Methyltyrosines; D019275:Radiopharmaceuticals