title: Pharmacokinetic analysis and uptake of 18F-FBPA-Fr after ultrasound-induced blood-brain barrier disruption for potential enhancement of boron delivery for neutron capture therapy.
abstract: Boronophenylalanine has been applied in clinical boron neutron capture therapy for the treatment of high-grade gliomas. The purpose of this study was to evaluate the pharmacokinetics of 4-borono-2-(18)F-fluoro-L-phenylalanine-fructose ((18)F-FBPA-Fr) in F98 glioma-bearing Fischer 344 rats by means of intravenous injection of (18)F-FBPA-Fr both with and without blood-brain barrier disruption (BBB-D) induced by focused ultrasound (FUS).
  
  
  METHODS
  Dynamic PET imaging of (18)F-FBPA-Fr was performed on the ninth day after tumor implantation. Blood samples were collected to obtain an arterial input function for tracer kinetic modeling. Ten animals were scanned for approximately 3 h to estimate the uptake of (18)F radioactivity with respect to time for the pharmacokinetic analysis. Rate constants were calculated by use of a 3-compartment model.
  
  
  RESULTS
  The accumulation of (18)F-FBPA-Fr in brain tumors and the tumor-to-contralateral brain ratio were significantly elevated after intravenous injection of (18)F-FBPA-Fr with BBB-D. (18)F-FBPA-Fr administration after sonication showed that the tumor-to-contralateral brain ratio for the sonicated tumors (3.5) was approximately 1.75-fold higher than that for the control tumors (2.0). Furthermore, the K1/k2 pharmacokinetic ratio after intravenous injection of (18)F-FBPA-Fr with BBB-D was significantly higher than that after intravenous injection without BBB-D.
  
  
  CONCLUSIONS
  This study demonstrated that radioactivity in tumors and the tumor-to-normal brain ratio after intravenous injection of (18)F-FBPA-Fr with sonication were significantly higher than those in tumors without sonication. The K1/k2 ratio may be useful for indicating the degree of BBB-D induced by FUS. Further studies are needed to determine whether FUS may be useful for enhancing the delivery of boronophenylalanine in patients with high-grade gliomas.
authors: Department of Biomedical Imaging and Radiological Sciences, School of Biomedical Science and Engineering, National Yang-Ming University, Taipei, Taiwan.
authors: Feng-Yi
authors: FY
authors: Yang
authors: Wen-Yuan
authors: WY
authors: Chang
authors: Jia-Je
authors: JJ
authors: Li
authors: Hsin-Ell
authors: HE
authors: Wang
authors: Jyh-Cheng
authors: JC
authors: Chen
authors: Chi-Wei
authors: CW
authors: Chang
mesh_terms: D000818:Animals; D017209:Apoptosis; D001812:Blood-Brain Barrier / Q000502:physiology* / Q000528:radiation effects; D001896:Boron Compounds / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics*; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism; D016503:Drug Delivery Systems; D005910:Glioma / Q000000981:diagnostic imaging / Q000378:metabolism; D006020:Glycopeptides / Q000493:pharmacokinetics*; D020287:In Situ Nick-End Labeling; D008297:Male; D009368:Neoplasm Transplantation; D017247:Neutron Capture Therapy / Q000379:methods*; D010649:Phenylalanine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D051381:Rats; D011916:Rats, Inbred F344; D014465:Ultrasonics
chemical_list: C504600:4-borono-2-fluorophenylalaninefructose; D001896:Boron Compounds; D006020:Glycopeptides; D019275:Radiopharmaceuticals; D010649:Phenylalanine; C033685:4-boronophenylalanine
keywords: 18F-FBPA-Fr; blood–brain barrier; boron neutron capture therapy; focused ultrasound; pharmacokinetics