title: 18F-FBPA as a tumor-specific probe of L-type amino acid transporter 1 (LAT1): a comparison study with18F-FDG and11C-Methionine PET.
abstract: OBJECTIVE
  The purpose of this study was to evaluate the usefulness of L-4-borono-2-18F-fluoro-phenylalanine (18F-FBPA) as a tumor-specific probe, in comparison to18F-FDG and11C-methionine (Met), focusing on its transport selectivity by L-type amino acid transporter 1 (LAT1), which is highly upregulated in cancers.
  
  
  METHODS
  Cellular analyses of FBPA were performed to evaluate the transportablity and Kmvalue. PET studies were performed in rat xenograft models of C6 glioma (n = 12) and in rat models of turpentine oil-induced subcutaneous inflammation (n = 9). The kinetic parameters and uptake values on static PET images were compared using the one-tissue compartment model (K1, k2) and maximum standardized uptake value (SUVmax).
  
  
  RESULTS
  The cellular analyses showed that FBPA had a lower affinity to a normal cell-type transporter LAT2 and induced less efflux through LAT2 among FBPA, Met, and BPA, while the efflux through LAT1 induced by FBPA was similar among the three compounds. The Kmvalue of18F-FBPA for LAT1 (196.8 ± 11.4 μM) was dramatically lower than that for LAT2 (2813.8 ± 574.5 μM), suggesting the higher selectivity of18F-FBPA for LAT1. K1and k2values were significantly smaller in18F-FBPA PET (K1= 0.04 ± 0.01 ml/ccm/min and k2= 0.07 ± 0.01 /min) as compared to11C-Met PET (0.22 ± 0.09 and 0.52 ± 0.10, respectively) in inflammatory lesions. Static PET analysis based on the SUVmax showed significantly higher accumulation of18F-FDG in the tumor and inflammatory lesions (7.2 ± 2.1 and 4.6 ± 0.63, respectively) as compared to both18F-FBPA (3.2 ± 0.40 and 1.9 ± 0.19) and11C-Met (3.4 ± 0.43 and 1.6 ± 0.11). No significant difference was observed between18F-FBPA and11C-Met in the static PET images.
  
  
  CONCLUSIONS
  This study shows the utility of18F-FBPA as a tumor-specific probe of LAT1 with low accumulation in the inflammatory lesions.
authors.affiliation: Department of Nuclear Medicine and Tracer Kinetics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan. watabe@tracer.med.osaka-u.ac.jp.|PET Molecular Imaging Center, Osaka University Graduate School of Medicine, Osaka, Japan. watabe@tracer.med.osaka-u.ac.jp.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Watabe
authors.affiliation: Department of Nuclear Medicine and Tracer Kinetics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: Hayato
authors.initials: H
authors.lastname: Ikeda
authors.affiliation: Department of Bio-system Pharmacology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Shushi
authors.initials: S
authors.lastname: Nagamori
authors.affiliation: Department of Bio-system Pharmacology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Pattama
authors.initials: P
authors.lastname: Wiriyasermkul
authors.affiliation: Department of Bio-system Pharmacology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Osaka University Graduate School of Medicine, Osaka University Hospital, Osaka University, Osaka, Japan.
authors.forename: Sadahiro
authors.initials: S
authors.lastname: Naka
authors.affiliation: PET Molecular Imaging Center, Osaka University Graduate School of Medicine, Osaka, Japan.|Department of Molecular Imaging in Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Yasukazu
authors.initials: Y
authors.lastname: Kanai
authors.affiliation: Department of Bio-system Pharmacology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Hagiwara
authors.affiliation: Department of Nuclear Medicine and Tracer Kinetics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: Masanao
authors.initials: M
authors.lastname: Aoki
authors.affiliation: Department of Nuclear Medicine and Tracer Kinetics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.|PET Molecular Imaging Center, Osaka University Graduate School of Medicine, Osaka, Japan.|Osaka University Graduate School of Medicine, Osaka University Hospital, Osaka University, Osaka, Japan.
authors.forename: Eku
authors.initials: E
authors.lastname: Shimosegawa
authors.affiliation: Department of Bio-system Pharmacology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Yoshikatsu
authors.initials: Y
authors.lastname: Kanai
authors.affiliation: Department of Nuclear Medicine and Tracer Kinetics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.|PET Molecular Imaging Center, Osaka University Graduate School of Medicine, Osaka, Japan.|Immunology Frontier Research Center, Osaka University, Osaka, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Hatazawa
mesh_terms: D000818:Animals; D001896:Boron Compounds / Q000493:pharmacokinetics*; D045744:Cell Line, Tumor; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D005910:Glioma / Q000000981:diagnostic imaging / Q000378:metabolism*; D027283:Large Neutral Amino Acid-Transporter 1 / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D008715:Methionine / Q000493:pharmacokinetics*; D057054:Molecular Imaging / Q000379:methods; D015336:Molecular Probe Techniques; D015335:Molecular Probes; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D011916:Rats, Inbred F344; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D001896:Boron Compounds; D027283:Large Neutral Amino Acid-Transporter 1; D015335:Molecular Probes; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; C072915:4-borono-2-fluorophenylalanine; D010649:Phenylalanine; C086242:carbon-11 methionine; D008715:Methionine
keywords: Glioma; Inflammation; LAT1; PET; Rat model