title: Real-time multi-modality imaging of glioblastoma tumor resection and recurrence.
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 non-invasive 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 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 multi-modality 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.
authors.affiliation: Molecular Neurotherapy and Imaging Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Shawn
authors.initials: S
authors.lastname: Hingtgen
authors.forename: Jose-Luiz
authors.initials: JL
authors.lastname: Figueiredo
authors.forename: Christian
authors.initials: C
authors.lastname: Farrar
authors.forename: Matthias
authors.initials: M
authors.lastname: Duebgen
authors.forename: Jordi
authors.initials: J
authors.lastname: Martinez-Quintanilla
authors.forename: Deepak
authors.initials: D
authors.lastname: Bhere
authors.forename: Khalid
authors.initials: K
authors.lastname: Shah
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001932:Brain Neoplasms / Q000601:surgery*; D045744:Cell Line, Tumor; D038524:Diffusion Magnetic Resonance Imaging; D004195:Disease Models, Animal; D005909:Glioblastoma / Q000601:surgery*; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008163:Luminescent Measurements; D051379:Mice; D008819:Mice, Nude; D009364:Neoplasm Recurrence, Local; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D019394:Ki-67 Antigen; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D049452:Green Fluorescent Proteins