title: Imaging and Selective Elimination of Glioblastoma Stem Cells with Theranostic Near-Infrared-Labeled CD133-Specific Antibodies.
abstract: Near-infrared photoimmunotherapy (NIR-PIT), which employs monoclonal antibody (mAb)-phototoxic phthalocyanine dye IR700 conjugates, permits the specific, image-guided and spatiotemporally controlled elimination of tumor cells. Here, we report the highly efficient NIR-PIT of human tumor xenografts initiated from patient-derived cancer stem cells (CSCs). Using glioblastoma stem cells (GBM-SCs) expressing the prototypic CSC marker AC133/CD133, we also demonstrate here for the first time that NIR-PIT is highly effective against brain tumors. The intravenously injected theranostic AC133 mAb conjugate enabled the non-invasive detection of orthotopic gliomas by NIR fluorescence imaging, and reached AC133+ GBM-SCs at the invasive tumor front. AC133-targeted NIR-PIT induced the rapid cell death of AC133+ GBM-SCs and thereby strong shrinkage of both subcutaneous and invasively growing brain tumors. A single round of NIR-PIT extended the overall survival of mice with established orthotopic gliomas by more than a factor of two, even though the harmless NIR light was applied through the intact skull. Humanised versions of this theranostic agent may facilitate intraoperative imaging and histopathological evaluation of tumor borders and enable the highly specific and efficient eradication of CSCs.
authors.affiliation: 1. Dept. for Radiation Oncology, University Hospital Freiburg, D-79106 Freiburg, Germany; 3. German Cancer Consortium (DKTK), Freiburg, and German Cancer Research Centre (DKFZ), D-69121 Heidelberg, Germany.
authors.forename: Hua
authors.initials: H
authors.lastname: Jing
authors.affiliation: 2. Radiology Medical Physics, University Hospital Freiburg, D-79106 Freiburg, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Weidensteiner
authors.affiliation: 2. Radiology Medical Physics, University Hospital Freiburg, D-79106 Freiburg, Germany.
authors.forename: Wilfried
authors.initials: W
authors.lastname: Reichardt
authors.affiliation: 1. Dept. for Radiation Oncology, University Hospital Freiburg, D-79106 Freiburg, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Gaedicke
authors.affiliation: 1. Dept. for Radiation Oncology, University Hospital Freiburg, D-79106 Freiburg, Germany; 3. German Cancer Consortium (DKTK), Freiburg, and German Cancer Research Centre (DKFZ), D-69121 Heidelberg, Germany.
authors.forename: Xuekai
authors.initials: X
authors.lastname: Zhu
authors.affiliation: 1. Dept. for Radiation Oncology, University Hospital Freiburg, D-79106 Freiburg, Germany; 3. German Cancer Consortium (DKTK), Freiburg, and German Cancer Research Centre (DKFZ), D-69121 Heidelberg, Germany.
authors.forename: Anca-Ligia
authors.initials: AL
authors.lastname: Grosu
authors.affiliation: 4. Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Hisataka
authors.initials: H
authors.lastname: Kobayashi
authors.affiliation: 1. Dept. for Radiation Oncology, University Hospital Freiburg, D-79106 Freiburg, Germany; 3. German Cancer Consortium (DKTK), Freiburg, and German Cancer Research Centre (DKFZ), D-69121 Heidelberg, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Niedermann
mesh_terms: D000071916:AC133 Antigen / Q000276:immunology*; D000818:Animals; D000906:Antibodies / Q000008:administration & dosage; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000628:therapy; D004195:Disease Models, Animal; D005909:Glioblastoma / Q000000981:diagnostic imaging* / Q000628:therapy*; D064593:Heterografts; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007211:Indoles / Q000008:administration & dosage; D054833:Isoindoles; D051379:Mice; D010789:Phototherapy / Q000379:methods*; D013234:Stem Cells / Q000276:immunology; D016019:Survival Analysis; D000068936:Theranostic Nanomedicine / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D000071916:AC133 Antigen; D000906:Antibodies; D007211:Indoles; D054833:Isoindoles; C000606024:Prom1 protein, mouse; C013647:phthalocyanine
keywords: CD133; cancer stem cells; glioblastoma; near-infrared photoimmunotherapy