title: Preparation and biological evaluation of 3-[(76)Br]bromo-α-methyl-L-tyrosine, a novel tyrosine analog for positron emission tomography imaging of tumors.
abstract: BACKGROUND
  3-[(18)F]fluoro-α-methyl-l-tyrosine ([(18)F]FAMT) is a useful amino acid tracer for positron emission tomography (PET) imaging of malignant tumors. FAMT analogs labeled with (76)Br, a positron emitter with a long half-life (t(1/2)=16.1 h), could potentially be widely used as amino acid tracers for tumor imaging. In this study, 3-[(76)Br]bromo-α-methyl-l-tyrosine ([(76)Br]BAMT) was designed, and its usefulness was evaluated as a novel PET tracer for imaging malignant tumors.
  
  
  METHODS
  In this study, both [(76)Br]BAMT and [(77)Br]BAMT were prepared. The in vitro and in vivo stability of [(77)Br]BAMT was evaluated by HPLC analysis. Cellular uptake and retention of [(77)Br]BAMT and [(18)F]FAMT were evaluated using LS180 colon adenocarcinoma cells. Biodistribution studies were performed in normal mice and in LS180 tumor-bearing mice, and the tumors were imaged with a small-animal PET scanner.
  
  
  RESULTS
  [(77)Br]BAMT was stable in vitro but was catabolized after administration in mice. Cellular accumulation and retention of [(77)Br]BAMT were significantly higher than those of [(18)F]FAMT. In biodistribution studies, the tumor accumulation of [(77)Br]BAMT was higher than that of [(18)F]FAMT. However, some level of debromination was seen, which caused more retention of radioactivity in the blood and organs than was seen with [(18)F]FAMT. PET imaging with [(76)Br]BAMT enabled clear visualization of the tumor, and the whole-body image using [(76)Br]BAMT was similar to that using [(18)F]FAMT.
  
  
  CONCLUSIONS
  [(77)Br]BAMT showed high levels of tumor accumulation, and [(76)Br]BAMT enabled clear visualization of the tumor by PET imaging. Although an improvement in stability is still needed, (76)Br-labeled FAMT analogs could potentially serve as PET tracers for the imaging of malignant tumors.
authors.affiliation: Medical Radioisotope Application Group, Quantum Beam Science Directorate, Japan Atomic Energy Agency, Watanuki, Takasaki, Gunma 370-1292, Japan. ohshima.yasuhiro@jaea.go.jp
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ohshima
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Hanaoka
authors.forename: Shigeki
authors.initials: S
authors.lastname: Watanabe
authors.forename: Yumi
authors.initials: Y
authors.lastname: Sugo
authors.forename: Satoshi
authors.initials: S
authors.lastname: Watanabe
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Tominaga
authors.forename: Noboru
authors.initials: N
authors.lastname: Oriuchi
authors.forename: Keigo
authors.initials: K
authors.lastname: Endo
authors.forename: Noriko S
authors.initials: NS
authors.lastname: Ishioka
mesh_terms: D000230:Adenocarcinoma / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001692:Biological Transport; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D015195:Drug Design; D004355:Drug Stability; D006801:Humans; D008297:Male; D051379:Mice; D049268:Positron-Emission Tomography / Q000379:methods*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics
chemical_list: C568678:3-bromo-alpha-methyltyrosine; D014443:Tyrosine