title: Preclinical evaluation of 2-amino-2-[11C]methyl-butanoic acid as a potential tumor-imaging agent in a mouse model.
abstract: OBJECTIVE
  C-labeled 2-amino-2-methyl-butanoic acid (Iva) was previously reported to provide high tumor uptake; however, the pharmacokinetic properties of C-labeled Iva have not been characterized. In the present study, we evaluated the potential of [C]Iva as a PET probe for tumor imaging.
  
  
  METHODS
  [C]Iva was incubated in mouse serum for 60 min at 37°C and then analyzed by high-performance liquid chromatography and thin-layer chromatography. In-vitro cellular uptake of [C]Iva was determined in PBS and sodium-free buffer at 37°C using SY human small-cell lung cancer cells. The effects of inhibitors of amino acid transporters on [C]Iva uptake were also determined in PBS. In-vivo distribution and dynamic PET studies were conducted in SY tumor-bearing mice.
  
  
  RESULTS
  [C]Iva was stable in mouse serum in vitro for 60 min. The cellular uptake of [C]Iva was linearly increased for 20 min in both PBS and sodium-free buffer and almost completely inhibited by an inhibitor of system L amino acid transporters and another of LAT1, a transporter of system L. In-vivo distribution and dynamic PET studies showed that [C]Iva was highly accumulated in tumor, but not in normal tissues, except for the pancreas and kidneys. The [C]Iva uptake ratio of tumor to several normal tissues, such as the lung, muscle, and brain, was high.
  
  
  CONCLUSIONS
  [C]Iva was stable in mouse serum and transported through system L amino acid transporters including LAT1, which is highly expressed in several tumors. [C]Iva is a promising PET probe for noninvasive tumor imaging.
authors.affiliation: aDiagnostic Imaging Program bMolecular Probe Program, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba cDepartment of Molecular Imaging, Medical Photonics Research Center, Hamamatsu University School of Medicine, Shizuoka dDepartment of Integrative Brain Imaging, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Chie
authors.initials: C
authors.lastname: Suzuki
authors.forename: Atsushi B
authors.initials: AB
authors.lastname: Tsuji
authors.forename: Koichi
authors.initials: K
authors.lastname: Kato
authors.forename: Hitomi
authors.initials: H
authors.lastname: Sudo
authors.forename: Ming-Rong
authors.initials: MR
authors.lastname: Zhang
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Saga
mesh_terms: D000818:Animals; D001692:Biological Transport; D002250:Carbon Radioisotopes; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004355:Drug Stability; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology*; D008297:Male; D051379:Mice; D049268:Positron-Emission Tomography / Q000379:methods*; D014018:Tissue Distribution; D014633:Valine / Q000378:metabolism / Q000493:pharmacokinetics
chemical_list: D002250:Carbon Radioisotopes; C032737:isovaline; D014633:Valine