title: Quantitative assessment of cerebral glucose metabolic rates after blood-brain barrier disruption induced by focused ultrasound using FDG-MicroPET.
abstract: The goal of this study was to evaluate the pharmacokinetics of (18)F-2-fluoro-2-deoxy-d-glucose ((18)F-FDG) and the expression of glucose transporter 1 (GLUT1) protein after blood-brain barrier (BBB) disruption of normal rat brains by focused ultrasound (FUS). After delivery of an intravenous bolus of ~37 MBq (1 mCi) (18)F-FDG, dynamic positron emission tomography scans were performed on rats with normal brains and those whose BBBs had been disrupted by FUS. Arterial blood sampling was collected throughout the scanning procedure. A 2-tissue compartmental model was used to estimate (18)F-FDG kinetic parameters in brain tissues. The rate constants Ki, K1, and k3 were assumed to characterize the uptake, transport, and hexokinase activity, respectively, of (18)F-FDG. The uptake of (18)F-FDG in brains significantly decreased immediately after the blood-brain barrier was disrupted. At the same time, the derived values of Ki, K1, and k3 for the sonicated brains were significantly lower than those for the control brains. In agreement with the reduction in glucose, Western blot analyses confirmed that focused ultrasound exposure significantly reduced the expression of GLUT1 protein in the brains. Furthermore, the effect of focused ultrasound on glucose uptake was transient and reversible 24h after sonication. Our results indicate that focused ultrasound may inhibit GLUT1 expression to decrease the glucose uptake in brain tissue during the period of BBB disruption.
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan; Biophotonics and Molecular Imaging Research Center, National Yang-Ming University, Taipei, Taiwan. Electronic address: fyyang@ym.edu.tw.
authors.forename: Feng-Yi
authors.initials: FY
authors.lastname: Yang
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Wen-Yuan
authors.initials: WY
authors.lastname: Chang
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan. Electronic address: jcchen@ym.edu.tw.
authors.forename: Jyh-Cheng
authors.initials: JC
authors.lastname: Chen
authors.affiliation: Department of Physical Medicine & Rehabilitation, Cheng Hsin General Hospital, Taipei, Taiwan.
authors.forename: Lin-Chien
authors.initials: LC
authors.lastname: Lee
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Yi-Shun
authors.initials: YS
authors.lastname: Hung
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D015153:Blotting, Western; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000096:biosynthesis; D019298:Glucose-6-Phosphate / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D008297:Male; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014463:Ultrasonography / Q000379:methods
chemical_list: D051272:Glucose Transporter Type 1; D019275:Radiopharmaceuticals; C047515:2-fluoro-2-deoxyglucose-6-phosphate; D019298:Glucose-6-Phosphate; D005947:Glucose
keywords: (18)F-FDG; Blood–brain barrier disruption; Focused ultrasound; MicroPET; Pharmacokinetics