Evgenii Belykh1, Jubran H Jubran1, Laeth L George1, Liudmila Bardonova1, Deborah R Healey2, Joseph F Georges3, Chad C Quarles2, Jennifer M Eschbacher4, Shwetal Mehta5, Adrienne C Scheck2, Peter Nakaji6, Mark C Preul7. 1. Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA. 2. Department of Neuro-Oncology Research, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA. 3. Department of Neurosurgery, Philadelphia College of Osteopathic Medicine, Philadelphia, PA, USA. 4. Department of Neuropathology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA. 5. Ivy Brain Tumor Center, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA. 6. Department of Neurosurgery, Banner Health-University of Arizona College of Medicine, Phoenix, AZ, USA. 7. Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA. Neuropub@barrowneuro.org.
Abstract
PURPOSE: This study evaluated the use of molecular imaging of fluorescent glucose analog 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (2-NBDG) as a discriminatory marker for intraoperative tumor border identification in a murine glioma model. PROCEDURES: 2-NBDG was assessed in GL261 and U251 orthotopic tumor-bearing mice. Intraoperative fluorescence of topical and intravenous 2-NBDG in normal and tumor regions was assessed with an operating microscope, handheld confocal laser scanning endomicroscope (CLE), and benchtop confocal laser scanning microscope (LSM). Additionally, 2-NBDG fluorescence in tumors was compared with 5-aminolevulinic acid-induced protoporphyrin IX fluorescence. RESULTS: Intravenously administered 2-NBDG was detectable in brain tumor and absent in contralateral normal brain parenchyma on wide-field operating microscope imaging. Intraoperative and benchtop CLE showed preferential 2-NBDG accumulation in the cytoplasm of glioma cells (mean [SD] tumor-to-background ratio of 2.76 [0.43]). Topically administered 2-NBDG did not create sufficient tumor-background contrast for wide-field operating microscope imaging or under benchtop LSM (mean [SD] tumor-to-background ratio 1.42 [0.72]). However, topical 2-NBDG did create sufficient contrast to evaluate cellular tissue architecture and differentiate tumor cells from normal brain parenchyma. Protoporphyrin IX imaging resulted in a more specific delineation of gross tumor margins than intravenous or topical 2-NBDG and a significantly higher tumor-to-normal-brain fluorescence intensity ratio. CONCLUSION: After intravenous administration, 2-NBDG selectively accumulated in the experimental brain tumors and provided bright contrast under wide-field fluorescence imaging with a clinical-grade operating microscope. Topical 2-NBDG was able to create a sufficient contrast to differentiate tumor from normal brain cells on the basis of visualization of cellular architecture with CLE. 5-Aminolevulinic acid demonstrated superior specificity in outlining tumor margins and significantly higher tumor background contrast. Given the nontoxicity of 2-NBDG, its use as a topical molecular marker for noninvasive in vivo intraoperative microscopy is encouraging and warrants further clinical evaluation.
PURPOSE: This study evaluated the use of molecular imaging of fluorescent glucose analog 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (2-NBDG) as a discriminatory marker for intraoperative tumor border identification in a murine glioma model. PROCEDURES: 2-NBDG was assessed in GL261 and U251 orthotopic tumor-bearing mice. Intraoperative fluorescence of topical and intravenous 2-NBDG in normal and tumor regions was assessed with an operating microscope, handheld confocal laser scanning endomicroscope (CLE), and benchtop confocal laser scanning microscope (LSM). Additionally, 2-NBDG fluorescence in tumors was compared with 5-aminolevulinic acid-induced protoporphyrin IX fluorescence. RESULTS: Intravenously administered 2-NBDG was detectable in brain tumor and absent in contralateral normal brain parenchyma on wide-field operating microscope imaging. Intraoperative and benchtop CLE showed preferential 2-NBDG accumulation in the cytoplasm of glioma cells (mean [SD] tumor-to-background ratio of 2.76 [0.43]). Topically administered 2-NBDG did not create sufficient tumor-background contrast for wide-field operating microscope imaging or under benchtop LSM (mean [SD] tumor-to-background ratio 1.42 [0.72]). However, topical 2-NBDG did create sufficient contrast to evaluate cellular tissue architecture and differentiate tumor cells from normal brain parenchyma. Protoporphyrin IX imaging resulted in a more specific delineation of gross tumor margins than intravenous or topical 2-NBDG and a significantly higher tumor-to-normal-brain fluorescence intensity ratio. CONCLUSION: After intravenous administration, 2-NBDG selectively accumulated in the experimental brain tumors and provided bright contrast under wide-field fluorescence imaging with a clinical-grade operating microscope. Topical 2-NBDG was able to create a sufficient contrast to differentiate tumor from normal brain cells on the basis of visualization of cellular architecture with CLE. 5-Aminolevulinic acid demonstrated superior specificity in outlining tumor margins and significantly higher tumor background contrast. Given the nontoxicity of 2-NBDG, its use as a topical molecular marker for noninvasive in vivo intraoperative microscopy is encouraging and warrants further clinical evaluation.
Authors: Matti Sievert; Konstantinos Mantsopoulos; Sarina K Mueller; Markus Eckstein; Robin Rupp; Marc Aubreville; Florian Stelzle; Nicolai Oetter; Andreas Maier; Heinrich Iro; Miguel Goncalves Journal: Acta Otorhinolaryngol Ital Date: 2022-02-07 Impact factor: 2.618
Authors: Jinhee Kim; So Young Baek; Stephen H Schlecht; Mélanie L Beaulieu; Lindsay Bussau; Junjie Chen; James A Ashton-Miller; Edward M Wojtys; Mark M Banaszak Holl Journal: J Exp Orthop Date: 2022-07-30
Authors: Yuan Xu; Irakliy Abramov; Evgenii Belykh; Giancarlo Mignucci-Jiménez; Marian T Park; Jennifer M Eschbacher; Mark C Preul Journal: Front Oncol Date: 2022-08-24 Impact factor: 5.738