Evaluation of Diagnostic Accuracy Following the Coadministration of Delta-Aminolevulinic Acid and Second Window Indocyanine Green in Rodent and Human Glioblastomas

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 to 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 (200mg/kg intraperitoneal) and SWIG (5mg/kg intravenous). Brain

5-aminolevulinic acid, fluorescein sodium, and indocyanine green for glioma margin detection: analysis of operating wide-field and confocal microscopy in glioma models of various grades

“…Earlier, our laboratory had used lower doses of 0.4 mg/kg, which were sufficient for confocal endomicroscopy ( 16 , 70 ), but in the current study, we found that a 0.4-mg/kg dose resulted in little if any tumor fluorescence under the operating microscope in infrared 800 mode. Other studies have shown that higher doses of ICG (5 mg/kg and 2.5 mg/kg) showed maximum fluorescence intensity and TBR at 1 hour after intravenous injection with an in vivo fluorescence imaging system through the intact skull, which correlates with our data ( 61 , 71 ). Lee’s group demonstrated that absolute ICG intensity in the tumor is less at 24 hours than at 1 hour; however, overall target/background ratio is somewhat more specific, likely because ICG clears from normal tissues.…”

Applications of indocyanine green in brain tumor surgery: review of clinical evidence and emerging technologies

“…Preresection ICG video angiography allowed for visualization of hemangioblastoma in all patients (8/8), whereas postresection video angiography confirmed complete resection in all patients (10/10). 28 Furthermore, because 5-ALA is a more established agent in the field of FGS, Cho et al 29 performed coadministration of 5-ALA and ICG in 4 patients with HGGs to benchmark the comparative performance of ICG. The two agents were found to have 90% concordant distributions and similar diagnostic accuracies, whereas tumor-associated necrosis demonstrated the most distinct difference,…”

“…25 mg ICG video angiography in 54 HGGs, 17 LGGs, 14 meningiomas, 12 metastases, & 3 hemangioblastomas can monitor blood flow in exposed tumoral & peritumoral vessels Zeh et al, 2017 9 HGG Mean SBR of 7.5 w/ 2.5-5.0 mg/kg SWIG in 10 pts, plateau of ICG NIRF up to 48 hrs postinfusion Cho et al, 2020 24 Newly diagnosed HGG showing weak or no protoporphyrin-IX fluorescence but strong SWIG fluorescence. 29 Another comparison study demonstrated that ICG was superior to 5-ALA in visualizing areas of increased angiogenesis, a process essential for metastasis of solid tumors. 30 Finally, ICG has applications in tumor surgeries when not used to directly localize the tumor.…”

Intraoperative molecular imaging: 3rd biennial clinical trials update

“…Furthermore, SWIG has 91% overall accuracy in predicting postoperative MRI by imaging the tumor cavity at the end of resection. 40 This technique can be used for brain metastases, intracranial meningiomas, and skull base tumors, among others. One of the limitations is visualization of melanoma metastases (ClinicalTrials.gov, no.…”