Maximal safe resection of malignant tissue is associated with improved progression-free survival and better response to radiation and chemotherapy for patients with glioblastoma (GBM). 5-Aminolevulinic acid (5-ALA) is the current FDA-approved standard for intraoperative brain tumor visualization. Unfortunately, autofluorescence in diffuse areas and high fluorescence in dense tissues significantly limit discrimination at tumor margins. This study is the first to compare 5-ALA to an investigational new drug, panitumumab-IRDye800CW, in the same animal model. A patient-derived GBM xenograft model was established in 16 nude mice, which later received injections of 5-ALA, panitumumab-IRDye800CW, IRDye800CW, 5-ALA and IRDye800CW, or 5-ALA and panitumumab-IRDye800CW. Brains were prepared for multi-instrument fluorescence imaging, IHC, and quantitative analysis of tumor-to-background ratio (TBR) and tumor margin accuracy. Statistical analysis was compared with Wilcoxon rank-sum or paired t test. Panitumumab-IRDye800CW had a 30% higher comprehensive TBR compared with 5-ALA (P = 0.0079). SDs for core and margin regions of interest in 5-ALA–treated tissues were significantly higher than those found in panitumumab-IRDye800CW–treated tissues (P = 0.0240 and P = 0.0284, respectively). Panitumumab-IRDye800CW specificities for tumor core and margin were more than 10% higher than those of 5-ALA. Higher AUC for panitumumab-IRDye800CW indicated strong capability to discriminate between normal and malignant brain tissue when compared with 5-ALA. This work demonstrates that panitumumab-IRDye800CW shows potential as a targeting agent for fluorescence intraoperative detection of GBM. Improved margin definition and surgical resection using panitumumab-IRDye800 has the potential to improve surgical outcomes and survival in patients with GBM compared with 5-ALA.

中文翻译：

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帕尼单抗-IRDye800CW 和 5-氨基乙酰丙酸在多形性胶质母细胞瘤模型中提供光学对比度的比较

恶性组织的最大安全切除与改善的无进展生存期和对胶质母细胞瘤 (GBM) 患者更好的放疗和化疗反应相关。5-氨基乙酰丙酸 (5-ALA) 是目前 FDA 批准的术中脑肿瘤可视化标准。不幸的是，弥散区域的自发荧光和致密组织中的高荧光显着限制了肿瘤边缘的区分。本研究首次在同一动物模型中将 5-ALA 与研究性新药帕尼单抗-IRDye800CW 进行比较。在 16 只裸鼠中建立了源自患者的 GBM 异种移植模型，随后分别注射了 5-ALA、帕尼单抗-IRDye800CW、IRDye800CW、5-ALA 和 IRDye800CW，或 5-ALA 和帕尼单抗-IRDye800CW。大脑准备用于多仪器荧光成像、IHC、肿瘤背景比 (TBR) 和肿瘤边缘准确性的定量分析。统计分析与 Wilcoxon 秩和或配对 t 检验进行比较。与 5-ALA 相比，帕尼单抗-IRDye800CW 的综合 TBR 高 30%（P = 0.0079）。5-ALA 处理的组织中感兴趣的核心和边缘区域的 SD 显着高于帕尼单抗-IRDye800CW 处理的组织（分别为 P = 0.0240 和 P = 0.0284）。Panitumumab-IRDye800CW 对肿瘤核心和边缘的特异性比 5-ALA 高 10% 以上。与 5-ALA 相比，帕尼单抗-IRDye800CW 的较高 AUC 表明区分正常和恶性脑组织的能力强。这项工作表明，帕尼单抗-IRDye800CW 显示出作为 GBM 术中荧光检测靶向剂的潜力。