Journal Article In vivo imaging of blood–brain barrier permeability using positron emission tomography with 2-amino-[3-11C]isobutyric acid

Okada, Maki  ,  Kikuchi, Tatsuya  ,  Okamura, Toshimitsu  ,  Ikoma, Yoko  ,  Tsuji, Atsushi  ,  Wakizaka, Hidekatsu  ,  Aoki, Ichio  ,  Ming-Rong, Zhang  ,  Kato, Koichi  ,  Kamakura, Tomoo

36 ( 12 )  , pp.1239 - 1248 , 2015-12 , Lippincott Williams & Wilkins
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 non-invasive, highly sensitive and quantitative method for evaluating the changes in BBB permeability induced by such techniques is needed to optimise treatment protocols. We evaluated 2-amino-[3-11C]isobutyric acid ([3-11C]AIB) as a positron emission tomography (PET) probe for quantifying BBB permeability in model rats.BBB opening was induced by a lipopolysaccharide injection or focused ultrasound (FUS) sonication. [3-11C]AIB distribution in the brain was evaluated by autoradiography and PET and compared with that of Evans blue (EB), a traditional BBB permeability marker. Kinetics of [3-11C]AIB was compared with that of gadolinium–diethylenetriamine pentaacetic acid (Gd-DTPA)-enhanced magnetic resonance imaging. The unidirectional blood–brain transfer constant (Ki) of [3-11C]AIB was estimated using Patlak plot.[3-11C]AIB uptake in the lesion area was significantly higher than that in the control area, and radioactivity co-localised with EB in both models. [3-11C]AIB uptake in the FUS-sonicated region decreased over time after sonication. The ratio of [3-11C]AIB accumulation in the FUS-treated to the contralateral side increased during the experiment time, whereas that of Gd-DTPA intensity reached a maximum at 10 min post-injection and decreased thereafter. The [3-11C]AIB Ki values were significantly higher in the lesion area than the control area.[3-11C]AIB PET is a promising, highly sensitive and quantitative imaging method for assessing BBB permeability.

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