Evaluation of Diagnostic Accuracy Following the Coadministration of Delta-Aminolevulinic Acid and Second Window Indocyan
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RESEARCH ARTICLE
Evaluation of Diagnostic Accuracy Following the Coadministration of Delta-Aminolevulinic Acid and Second Window Indocyanine Green in Rodent and Human Glioblastomas Steve S. Cho,1,2 Saad Sheikh,3 Clare W. Teng,1,2 Joseph Georges,4,5 Andrew I. Yang,1 Emma De Ravin,1,2 Love Buch,1 Carrie Li,1,2 Yash Singh,1 Denah Appelt,4 Edward J. Delikatny,6 E. James Petersson,7 Andrew Tsourkas,8 Jay Dorsey,3 Sunil Singhal,9 John Y. K. Lee 1 1
Department of Neurosurgery, Hospital of the University of Pennsylvania, Philadelphia, PA, USA Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA 3 Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA 4 Department of Biomedical Sciences, Philadelphia College of Osteopathic Medicine, Philadelphia, PA, USA 5 Department of Neurosurgery, Philadelphia College of Osteopathic Medicine, Philadelphia, PA, USA 6 Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA 7 Department of Chemistry, University of Pennsylvania, Philadelphia, PA, USA 8 Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA 9 Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA, USA 2
Abstract Purpose: Fluorescence-guided-surgery offers intraoperative visualization of neoplastic tissue. Delta-aminolevulinic acid (5-ALA), which targets enzymatic abnormality in neoplastic cells, is the only approved agent for fluorescence-guided neurosurgery. More recently, we described Second Window Indocyanine Green (SWIG) which targets neoplastic tissue through enhanced vascular permeability. We hypothesized that SWIG would demonstrate similar clinical utility in identification of high-grade gliomas compared with 5-ALA. Procedures: Female C57/BL6 and nude/athymic mice underwent intracranial implantation of 300,000 GL261 and U87 cells, respectively. Tumor-bearing mice were euthanized after administration of 5-ALA (200 mg/kg intraperitoneal) and SWIG (5 mg/kg intravenous). Brain sections were imaged for protoporphyrin-IX and ICG fluorescence. Fluorescence and H&E images were registered using semi-automatic scripts for analysis. Human subjects with HGG were administered SWIG (2.5 mg/kg intravenous) and 5-ALA (20 mg/kg oral). Intraoperatively, tumors were imaged for ICG and protoporphyrin-IX fluorescence.
Correspondence to: John Lee; e-mail: [email protected]
Cho S.S. et al.: Evaluation of Diagnostic Accuracy
Results: In non-necrotic tumors, 5-ALA and SWIG demonstrated 90.2 % and 89.2 % tumor accuracy (p value = 0.52) in U87 tumors and 88.1 % and 87.7 % accuracy (p value = 0.83) in GL261 tumors. The most distinct difference between 5-ALA and SWIG distribution was seen in areas of tumor-associated necrosis, which often showed weak/no protoporphyrin-IX fluorescence, but strong SWIG fluorescence. In twenty biopsy specimens from four subjects with HGG, SWIG demonstrated 100 % accuracy, while 5-ALA demonstrated 75–85 % accuracy; there was 90 % concordance between SWIG and
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