title: Micro-SPECT/CT-based pharmacokinetic analysis of 99mTc-diethylenetriaminepentaacetic acid in rats with blood-brain barrier disruption induced by focused ultrasound.
abstract: This study evaluated the pharmacokinetics of (99m)Tc-diethylenetriamine pentaacetate acid ((99m)Tc-DTPA) after intravenous administration in healthy and F98 glioma-bearing F344 rats in the presence of blood-brain barrier disruption (BBB-D) induced by focused ultrasound (FUS). The pharmacokinetics of the healthy and tumor-containing brains after BBB-D were compared to identify the optimal time period for combined treatment.
  
  
  METHODS
  Healthy and F98 glioma-bearing rats were injected intravenously with Evans blue (EB) and (99m)Tc-DTPA; these treatments took place with or without BBB-D induced by transcranial FUS of 1 hemisphere of the brain. The permeability of the BBB was quantified by EB extravasation. Twelve rats were scanned for 2 h to estimate uptake of (99m)Tc radioactivity with respect to time for the pharmacokinetic analysis. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining was performed to examine tissue damage.
  
  
  RESULTS
  The accumulations of EB and (99m)Tc-DTPA in normal brains or brains with a tumor were significantly elevated after the intravenous injection when BBB-D was induced. The disruption-to-nondisruption ratio of the brains and the tumor-to-ipsilateral brain ratio of the tumors in terms of radioactivity reached a peak at 45 and 60 min, respectively. EB injection followed by sonication showed that there was an increase of about 2-fold in the tumor-to-ipsilateral brain EB ratio of the target tumors (7.36), compared with the control tumors (3.73). TUNEL staining showed no significant differences between the sonicated tumors and control tumors.
  
  
  CONCLUSIONS
  This study demonstrates that (99m)Tc-DTPA micro-SPECT/CT can be used for the pharmacokinetic analysis of BBB-D induced by FUS. This method should be able to provide important information that will help with establishing an optimal treatment protocol for drug administration after FUS-induced BBB-D in clinical brain disease therapy.
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan. fyyang@ym.edu.tw
authors.forename: Feng-Yi
authors.initials: FY
authors.lastname: Yang
authors.forename: Hsin-Ell
authors.initials: HE
authors.lastname: Wang
authors.forename: Guan-Liang
authors.initials: GL
authors.lastname: Lin
authors.forename: Ming-Che
authors.initials: MC
authors.lastname: Teng
authors.forename: Hui-Hsien
authors.initials: HH
authors.lastname: Lin
authors.forename: Tai-Tong
authors.initials: TT
authors.lastname: Wong
authors.forename: Ren-Shyan
authors.initials: RS
authors.lastname: Liu
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000528:radiation effects; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism*; D045744:Cell Line, Tumor; D005910:Glioma / Q000000981:diagnostic imaging / Q000378:metabolism*; D008657:Metabolic Clearance Rate; D009928:Organ Specificity; D051381:Rats; D011916:Rats, Inbred F344; D013010:Sonication; D016284:Technetium Tc 99m Pentetate / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed
chemical_list: D016284:Technetium Tc 99m Pentetate