Real-time multi-modality imaging of glioblastoma tumor resection and recurrence
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LABORATORY INVESTIGATION
Real-time multi-modality imaging of glioblastoma tumor resection and recurrence Shawn Hingtgen • Jose-Luiz Figueiredo • Christian Farrar Matthias Duebgen • Jordi Martinez-Quintanilla • Deepak Bhere • Khalid Shah
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Received: 5 June 2012 / Accepted: 21 November 2012 / Published online: 16 December 2012 Ó Springer Science+Business Media New York 2012
Abstract The lack of relevant pre-clinical animal models incorporating the clinical scenario of Glioblastoma multiforme (GBM) resection and recurrence has contributed significantly to the inability to successfully treat GBM. A multi-modality imaging approach that allows real-time assessment of tumor resection during surgery and noninvasive detection of post-operative tumor volumes is urgently needed. In this study, we report the development and implementation of an optical imaging and magnetic resonance imaging (MRI) approach to guide GBM resection during surgery and track tumor recurrence at multiple
Shawn Hingtgen and Jose-Luiz Figueiredo contributed equally to this work.
Electronic supplementary material The online version of this article (doi:10.1007/s11060-012-1008-z) contains supplementary material, which is available to authorized users. S. Hingtgen J.-L. Figueiredo M. Duebgen J. Martinez-Quintanilla D. Bhere K. Shah (&) Molecular Neurotherapy and Imaging Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA e-mail: [email protected] C. Farrar Department of Radiology, Massachusetts General Hospital, Athinoula A. Martinos Center for Biomedical Imaging, Harvard Medical School, Boston, MA 02114, USA K. Shah Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA K. Shah Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA
resolutions in mice. Intra-operative fluorescence-guided surgery allowed real-time monitoring of intracranial tumor removal and led to greater than 90 % removal of established intracranial human GBM. The fluorescent signal clearly delineated tumor margins, residual tumor, and correlated closely with the clinically utilized fluorescence surgical marker 5-aminolevulinic acid/porphyrin. Post-operative non-invasive optical imaging and MRI confirmed near-complete tumor removal, which was further validated by immunohistochemistry (IHC). Longitudinal non-invasive imaging and IHC showed rapid recurrence of multi-focal tumors that exhibited a faster growth rate and altered blood-vessel density compared to non-resected tumors. Surgical tumor resection significantly extended long-term survival, however mice ultimately succumbed to the recurrent GBM. This multimodality imaging approach to GBM resection and recurrence in mice should provide an important platform for investigating multiple aspects of GBM and ultimately evaluating novel therapeutics. Keywords Glioma Image-Guided resection In vivo imaging Recurrence
Introduction Glioblastoma multiforme (GBM) is the most common primary brain cancer in adults [1]. G
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