title: Pharmacokinetic analysis of 111 in-labeled liposomal Doxorubicin in murine glioblastoma after blood-brain barrier disruption by focused ultrasound.
abstract: The goal of this study was to evaluate the pharmacokinetics of targeted and untargeted (111)In-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. (111)In-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 (111)In-AP-1 Lipo-Dox or (111)In-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 (111)In-AP-1 Lipo-Dox with sonication. The (111)In-liposomes micro-SPECT/CT should be able to provide important information about the optimum therapeutic window for the chemotherapy of brain tumors using sonication.
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: Ren-Shyan
authors.initials: RS
authors.lastname: Liu
authors.forename: Ming-Che
authors.initials: MC
authors.lastname: Teng
authors.forename: Jia-Je
authors.initials: JJ
authors.lastname: Li
authors.forename: Maggie
authors.initials: M
authors.lastname: Lu
authors.forename: Ming-Cheng
authors.initials: MC
authors.lastname: Wei
authors.forename: Tai-Tong
authors.initials: TT
authors.lastname: Wong
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D005909:Glioblastoma / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D007205:Indium Radioisotopes; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D064847:Multimodal Imaging; D049268:Positron-Emission Tomography; D013010:Sonication; D014057:Tomography, X-Ray Computed; D023041:Xenograft Model Antitumor Assays
chemical_list: D007205:Indium Radioisotopes; D004317:Doxorubicin