title: In-vivo imaging of blood-brain barrier permeability using positron emission tomography with 2-amino-[3-11C]isobutyric acid.
abstract: OBJECTIVE
  The blood-brain barrier (BBB) limits the entry of some therapeutics into the brain, resulting in reduced efficacy. BBB-opening techniques have been developed to enhance the entry into the brain. However, a noninvasive, highly sensitive and quantitative method for evaluating the changes in BBB permeability induced by such techniques is needed to optimize treatment protocols. We evaluated 2-amino-[3-C]isobutyric acid ([3-C]AIB) as a PET probe to quantify BBB permeability in model rats.
  
  
  METHODS
  BBB opening was induced by a lipopolysaccharide injection or focused ultrasound (FUS) sonication. [3-C]AIB distribution in the brain was evaluated by autoradiography and PET and compared with that of Evans blue, a traditional BBB permeability marker. Kinetics of [3-C]AIB was compared with that of gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA)-enhanced MRI. The unidirectional blood-brain transfer constant (Ki) of [3-C]AIB was estimated using the Patlak plot.
  
  
  RESULTS
  [3-C]AIB uptake in the lesion area was significantly higher than that in the control area and radioactivity colocalized with Evans blue in both models. [3-C]AIB uptake in the FUS-sonicated region decreased over time after sonication. The ratio of [3-C]AIB accumulation in the FUS-treated to the contralateral side increased during the experimental period, whereas that of the Gd-DTPA intensity reached a maximum at 10 min after injection and decreased thereafter. The [3-C]AIB Ki values were significantly higher in the lesion area than the control area.
  
  
  CONCLUSIONS
  [3-C]AIB PET is a promising, highly sensitive and quantitative imaging method for assessment of BBB permeability.
authors.affiliation: aMolecular Imaging Centre, National Institute of Radiological Sciences, Chiba bCentre for Industrial and Governmental Relations, The University of Electro-Communications cDepartment of Integrative Brain Imaging, National Centre of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Okada
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kikuchi
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Okamura
authors.forename: Yoko
authors.initials: Y
authors.lastname: Ikoma
authors.forename: Atsushi B
authors.initials: AB
authors.lastname: Tsuji
authors.forename: Hidekatsu
authors.initials: H
authors.lastname: Wakizaka
authors.forename: Tomoo
authors.initials: T
authors.lastname: Kamakura
authors.forename: Ichio
authors.initials: I
authors.lastname: Aoki
authors.forename: Ming-Rong
authors.initials: MR
authors.lastname: Zhang
authors.forename: Koichi
authors.initials: K
authors.lastname: Kato
mesh_terms: D000621:Aminoisobutyric Acids / Q000097:blood; D000818:Animals; D001158:Arteries / Q000378:metabolism; D001345:Autoradiography; D001812:Blood-Brain Barrier / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D010539:Permeability / Q000187:drug effects; D049268:Positron-Emission Tomography; D051381:Rats; D017207:Rats, Sprague-Dawley; D014463:Ultrasonography
chemical_list: D000621:Aminoisobutyric Acids; D008070:Lipopolysaccharides; C100049:2-aminoisobutyric acid