Pharmacokinetic changes induced by focused ultrasound in glioma-bearing rats as measured by dynamic contrast-enhanced MRI

PLoS One. 2014 Mar 26;9(3):e92910. doi: 10.1371/journal.pone.0092910. eCollection 2014.

Abstract

Focused ultrasound (FUS) combined with microbubbles has been shown to be a noninvasive and targeted drug delivery technique for brain tumor treatment. The purpose of this study was to measure the kinetics of Gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) in glioma-bearing rats in the presence of FUS-induced blood-brain barrier disruption (BBB-D) by magnetic resonance imaging (MRI). A total of ten glioma-bearing rats (9-12 weeks, 290-340 g) were used in this study. Using dynamic contrast-enhanced (DCE)-MRI, the spatial permeability of FUS-induced BBB-D was evaluated and the kinetic parameters were calculated by a general kinetic model (GKM). The results demonstrate that the mean Ktrans of the sonicated tumor (0.128±0.019 at 20 min and 0.103±0.023 at 24 h after sonication, respectively) was significantly higher than (2.46-fold at 20 min and 1.78-fold at 24 h) that of the contralateral (non-sonicated) tumor (0.052±0.019 at 20 min and 0.058±0.012 at 24 h after sonication, respectively). In addition, the transfer constant Ktrans in the sonicated tumor correlated strongly with tissue EB extravasation (R = 0.95), which suggests that DCE-MRI may reflect drug accumulation in the brain. Histological observations showed no macroscopic damage except for a few small erythrocyte extravasations. The current study demonstrates that DCE-MRI can monitor the dynamics of the FUS-induced BBB-D process and constitutes a useful tool for quantifying BBB permeability in tumors.

MeSH terms

  • Animals
  • Blood-Brain Barrier / diagnostic imaging
  • Blood-Brain Barrier / pathology
  • Brain Neoplasms / diagnostic imaging*
  • Contrast Media / pharmacokinetics*
  • Evans Blue / metabolism
  • Extravasation of Diagnostic and Therapeutic Materials / diagnostic imaging
  • Gadolinium DTPA / pharmacokinetics
  • Glioma / diagnostic imaging*
  • Glioma / pathology
  • Magnetic Resonance Imaging*
  • Male
  • Rats, Inbred F344
  • Sonication
  • Ultrasonics*
  • Ultrasonography

Substances

  • Contrast Media
  • Evans Blue
  • Gadolinium DTPA

Grant support

The authors have no support or funding to report.