Theranostics 2016; 6(6):862-874. doi:10.7150/thno.12890

Research Paper

Imaging and Selective Elimination of Glioblastoma Stem Cells with Theranostic Near-Infrared-Labeled CD133-Specific Antibodies

Hua Jing1,3, Claudia Weidensteiner2, Wilfried Reichardt2, Simone Gaedicke1, Xuekai Zhu1,3, Anca-Ligia Grosu1,3, Hisataka Kobayashi4, Gabriele Niedermann1,3✉

1. Dept. for Radiation Oncology, University Hospital Freiburg, D-79106 Freiburg, Germany
2. Radiology Medical Physics, University Hospital Freiburg, D-79106 Freiburg, Germany
3. German Cancer Consortium (DKTK), Freiburg, and German Cancer Research Centre (DKFZ), D-69121 Heidelberg, Germany
4. Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA

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.

Keywords: near-infrared photoimmunotherapy, cancer stem cells, CD133, glioblastoma

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How to cite this article:
Jing H, Weidensteiner C, Reichardt W, Gaedicke S, Zhu X, Grosu AL, Kobayashi H, Niedermann G. Imaging and Selective Elimination of Glioblastoma Stem Cells with Theranostic Near-Infrared-Labeled CD133-Specific Antibodies. Theranostics 2016; 6(6):862-874. doi:10.7150/thno.12890. Available from http://www.thno.org/v06p0862.htm