Resection and survival data from a clinical trial of glioblastoma multiforme‐specific IRDye800‐BBN fluorescence‐guided surgery

Abstract

Supra-maximum surgical tumor resection without neurological damage is highly valuable for treatment and prognosis of patients with glioblastoma multiforme (GBM). We developed a GBM-specific fluorescence probe using IRDye800CW (peak absorption/ emission, 778/795 nm) and bombesin (BBN), which (IRDye800-BBN) targets the gastrin-releasing peptide receptor, and evaluated the image-guided resection efficiency, sensitivity, specificity, and survivability. Twenty-nine patients with newly diagnosed GBM were enrolled. Sixteen hours preoperatively, IRDye800-BBN (1 mg in 20 ml sterile water) was intravenously administered. A customized fluorescence surgical navigation system was used intraoperatively. Postoperatively, enhanced magnetic resonance images were used to assess the residual tumor volume, calculate the resection extent, and confirm whether complete resection was achieved. Tumor tissues and nonfluorescent brain tissue in adjacent noneloquent boundary areas were harvested and assessed for diagnostic accuracy. Complete resection was achieved in 82.76% of patients. The median extent of resection was 100% (range, 90.6-100%). Eighty-nine samples were harvested, including 70 fluorescence-positive and 19 fluorescencenegative samples. The sensitivity and specificity of IRDye800-BBN were 94.44% (95% CI, 85.65-98.21%) and 88.24% (95% CI, 62.25-97.94%), respectively. Twenty-five Kunshan He, Chongwei Chi, Deling Li, and Jingjing Zhang authors contributed equally to this work.

Bombesin Receptor Family Activation and CNS/Neural Tumors: Review of Evidence Supporting Possible Role for Novel Targeted Therapy

“…Two studies have used a different approach to visualizing BnRs on gliomas by forming fluorescence BnR-conjugated PET ligands, which can be used preoperatively or at surgery (173,174). The BnR ligand 68 Ga-IRDye800CW-BBN is a PET/near-infrared fluorescence (NIRF) dual-imaging modality GRPR ligand developed to fulfil these two requirements.…”

Receptor-Targeted Fluorescence-Guided Surgery With Low Molecular Weight Agents

“…Of note, the authors reported that the approach was not optimal for deep-seated tumors as signal-tobackground ratios were not adequate during surgery in some instances. In another study, He et al (53) investigated the extent of resection and survivability using BBN-IRdye800CW in 29 patients. To avoid confounding variability due to inter-surgeon differences, all procedures were performed by the same surgeon.…”

“…Intraoperative glioblastoma multiforme imaging with 1 mg total BBN-IRdye800CW administered 16 h prior to surgery: NIRF prior to resection (B) , residual fluorescence after initial tumor removal (C) and tumor-cavity after complete resection (D) . Panels (B–D) are adapted from ( 53 ) with permission.…”

“…In another study, He et al. ( 53 ) investigated the extent of resection and survivability using BBN-IRdye800CW in 29 patients. To avoid confounding variability due to inter-surgeon differences, all procedures were performed by the same surgeon.…”

Fluorine-18-Labeled Fluorescent Dyes for Dual-Mode Molecular Imaging

“…Using fluorescence-guided resection, no tumor regrowth was observed compared to resection performed under bright light. The efficacy of fluorescence-guided resection has also been observed in several clinical trials, underscoring the need for a single compound that could potentially be used for diagnostic, guided surgery and post-surgical assessment [ 136 , 137 ]. Another advantage of fluorescence in cancer management resides in the use of tracer’s emission for intraoperative frozen section histology, which consists in imaging resected tissue sections during surgery to assess if tumorous tissues are remaining [ 138 ].…”