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  • Title: In-vivo imaging of blood-brain barrier permeability using positron emission tomography with 2-amino-[3-11C]isobutyric acid.
    Author: Okada M, Kikuchi T, Okamura T, Ikoma Y, Tsuji AB, Wakizaka H, Kamakura T, Aoki I, Zhang MR, Kato K.
    Journal: Nucl Med Commun; 2015 Dec; 36(12):1239-48. PubMed ID: 26397998.
    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. CONCLUSION: [3-C]AIB PET is a promising, highly sensitive and quantitative imaging method for assessment of BBB permeability.
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