Pharmacokinetic Analysis of 111In-Labeled Liposomal Doxorubicin in Murine Glioblastoma after Blood-Brain Barrier Disruption by Focused Ultrasound

Feng Yi Yang, Hsin Ell Wang, Ren Shyan Liu, Ming Che Teng, Jia Je Li, Maggie Lu, Ming Cheng Wei, Tai-Tong Wong

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48 Citations (Scopus)


The goal of this study was to evaluate the pharmacokinetics of targeted and untargeted 111In-doxorubicin liposomes after these have been intravenously administrated to tumor-bearing mice in the presence of blood-brain barrier disruption (BBB-D) induced by focused ultrasound (FUS). An intracranial brain tumor model in NOD-scid mice using human brain glioblastoma multiforme (GBM) 8401 cells was developed in this study. 111In-labeled human atherosclerotic plaque-specific peptide-1 (AP-1)-conjugated liposomes containing doxorubicin (Lipo-Dox; AP-1 Lipo-Dox) were used as a microSPECT probe for radioactivity measurements in the GBM-bearing mice. Compared to the control tumors treated with an injection of 111In-AP-1 Lipo-Dox or 111In-Lipo-Dox, the animals receiving the drugs followed by FUS exhibited enhanced accumulation of the drug in the brain tumors (p<0.05). Combining sonication with drugs significantly increased the tumor-to-normal brain doxorubicin ratio of the target tumors compared to the control tumors. The tumor-to-normal brain ratio was highest after the injection of 111In-AP-1 Lipo-Dox with sonication. The 111In-liposomes micro-SPECT/CT should be able to provide important information about the optimum therapeutic window for the chemotherapy of brain tumors using sonication.

Original languageEnglish
Article numbere45468
JournalPLoS One
Issue number9
Publication statusPublished - Sep 18 2012
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)


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