title: Development of a Widely Usable Amino Acid Tracer: ⁷⁶Br-α-Methyl-Phenylalanine for Tumor PET Imaging.
abstract: Radiolabeled amino acids are superior PET tracers for the imaging of malignant tumors, and amino acids labeled with (76)Br, an attractive positron emitter because of its relatively long half-life (16.2 h), could potentially be a widely usable tumor imaging tracer. In this study, in consideration of its stability and tumor specificity, we designed two (76)Br-labeled amino acid derivatives, 2-(76)Br-bromo-α-methyl-l-phenylalanine (2-(76)Br-BAMP) and 4-(76)Br-bromo-α-methyl-l-phenylalanine (4-(76)Br-BAMP), and investigated their potential as tumor imaging agents.
  
  
  METHODS
  Both (76)Br- and (77)Br-labeled amino acid derivatives were prepared. We performed in vitro and in vivo stability studies and cellular uptake studies using the LS180 colon adenocarcinoma cell line. Biodistribution studies in normal mice and in LS180 tumor-bearing mice were performed, and the tumors were imaged with a small-animal PET scanner.
  
  
  RESULTS
  Both (77)Br-BAMPs were stable in the plasma and in the murine body. Although both (77)Br-BAMPs were taken up by LS180 cells and the uptake was inhibited by L-type amino acid transporter 1 inhibitors, 2-(77)Br-BAMP exhibited higher uptake than 4-(77)Br-BAMP. In the biodistribution studies, 2-(77)Br-BAMP showed more rapid blood clearance and lower renal accumulation than 4-(77)Br-BAMP. More than 90% of the injected radioactivity was excreted in the urine by 6 h after the injection of 2-(77)Br-BAMP. High tumor accumulation of 2-(77)Br-BAMP was observed in tumor-bearing mice, and PET imaging with 2-(76)Br-BAMP enabled clear visualization of the tumors.
  
  
  CONCLUSIONS
  2-(77)Br-BAMP exhibited preferred pharmacokinetics and high LS180 tumor accumulation, and 2-(76)Br-BAMP enabled clear visualization of the tumors by PET imaging. These findings suggest that 2-(76)Br-BAMP could constitute a potential new PET tracer for tumor imaging and may eventually enable the wider use of amino acid tracers.
authors: Department of Bioimaging Information Analysis, Gunma University Graduate School of Medicine, Maebashi, Japan Department of Molecular Imaging and Radiotherapy, Graduate School of Pharmaceutical Science, Chiba University, Chiba, Japan hanaokah@gunma-u.ac.jp.
authors: Hirofumi
authors: H
authors: Hanaoka
authors: Medical Radioisotope Application Group, Life Science and Biotechnology Division, Quantum Beam Science Center, Research Department of Nuclear Science, Japan Atomic Energy Agency, Takasaki, Japan.
authors: Yasuhiro
authors: Y
authors: Ohshima
authors: Department of Molecular Imaging and Radiotherapy, Graduate School of Pharmaceutical Science, Chiba University, Chiba, Japan.
authors: Yurika
authors: Y
authors: Suzuki
authors: Department of Bioimaging Information Analysis, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors: Aiko
authors: A
authors: Yamaguchi
authors: Medical Radioisotope Application Group, Life Science and Biotechnology Division, Quantum Beam Science Center, Research Department of Nuclear Science, Japan Atomic Energy Agency, Takasaki, Japan.
authors: Shigeki
authors: S
authors: Watanabe
authors: Department of Molecular Imaging and Radiotherapy, Graduate School of Pharmaceutical Science, Chiba University, Chiba, Japan.
authors: Tomoya
authors: T
authors: Uehara
authors: Division of Biosystem Pharmacology, Department of Pharmacology, Graduate School of Medicine, Osaka University, Suita, Japan; and.
authors: Shushi
authors: S
authors: Nagamori
authors: Division of Biosystem Pharmacology, Department of Pharmacology, Graduate School of Medicine, Osaka University, Suita, Japan; and.
authors: Yoshikatsu
authors: Y
authors: Kanai
authors: Medical Radioisotope Application Group, Life Science and Biotechnology Division, Quantum Beam Science Center, Research Department of Nuclear Science, Japan Atomic Energy Agency, Takasaki, Japan.
authors: Noriko S
authors: NS
authors: Ishioka
authors: Department of Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors: Yoshito
authors: Y
authors: Tsushima
authors: Department of Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors: Keigo
authors: K
authors: Endo
authors: Department of Molecular Imaging and Radiotherapy, Graduate School of Pharmaceutical Science, Chiba University, Chiba, Japan.
authors: Yasushi
authors: Y
authors: Arano
mesh_terms: D000230:Adenocarcinoma / Q000000981:diagnostic imaging* / Q000473:pathology; D000818:Animals; D001967:Bromine Radioisotopes; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology; D055808:Drug Discovery; D006801:Humans; D051379:Mice; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography / Q000379:methods*; D014018:Tissue Distribution
chemical_list: D001967:Bromine Radioisotopes; C012436:alpha-methylphenylalanine; D010649:Phenylalanine
keywords: 76Br; PET; tumor imaging; α-methyl-l-phenylalanine