Journal
BIOENGINEERING & TRANSLATIONAL MEDICINE
Volume 6, Issue 1, Pages -Publisher
WILEY
DOI: 10.1002/btm2.10182
Keywords
fluorescent IRDye800-BBN; glioma; intraoperative; neurosurgery; prognosis
Funding
- Beijing Nova program [Z201100006820017, Z19111000110000]
- National Key R&D Program of China [2017YFA0205200, 2017YFC1309100, 2016YFC0103803, 2019YFC0120800, 2018YFC0910602, 2017YFA0700401]
- National Natural Science Foundation of China [81527805, 81971668, 61901472]
- Key Research Projects in Frontier Science of Chinese Academy of Sciences (CAS) [QYZDJ-SSW-JSC005, KFJ-STS-ZDTP-059]
- Capital characteristic Clinical Application Project [Z181100001718196]
- China Postdoctoral Science Foundation [2019M660409]
- Clinical Scientist Supporting grant of Beijing Tiantan Hospital [YSP201902]
- National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health
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The GBM-specific fluorescent IRDye800-BBN achieved a complete resection rate of 82.76% in 29 GBM patients, with a sensitivity and specificity of 94.44% and 88.24%, respectively. This specific fluorescence may help neurosurgeons accurately identify tumor boundaries and potentially improve patient survival outcomes.
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 fluorescence-negative 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 patients were followed up (median, 13.5 [3.1-36.0] months), and 14 had died. The mean preoperative and immediate and 6-month postoperative Karnofsky performance scores were 77.9 +/- 11.8, 71.3 +/- 19.2, and 82.6 +/- 14.7, respectively. The median overall and progression-free survival were 23.1 and 14.1 months, respectively. In conclusion, GBM-specific fluorescent IRDye800-BBN can help neurosurgeons identify the tumor boundary with sensitivity and specificity, and may improve survival outcomes.
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