短波红外成像技术在神经母细胞瘤高对比度荧光引导手术方面起到重要作用。
Short-wave infrared imaging enables high-contrast fluorescence-guided surgery in neuroblastoma.
发表日期:2023 Mar 19
作者:
Laura Privitera, Dale J Waterhouse, Alessandra Preziosi, Irene Paraboschi, Olumide Ogunlade, Chiara Da Pieve, Marta Barisa, Olumide Ogunbiyi, Gregory Weitsman, J Ciaran Hutchinson, Kate Cross, Lorenzo Biassoni, Danail Stoyanov, Neil Sebire, Paul Beard, Paolo De Coppi, Gabriela Kramer-Marek, John Anderson, Stefano Giuliani
来源:
CANCER RESEARCH
摘要:
荧光引导外科手术将在儿童肿瘤的术中管理中扮演关键角色。短波红外成像(SWIR)具有相对于传统近红外I(NIR-I)成像的优势,减少了组织散射和自发荧光。在此,将两种长尾发射SWIR范围的NIR-I染料(IRDye800CW和IR12)与临床级别的抗GD2单克隆抗体(Dinutuximab-beta)结合,以对比神经母细胞瘤手术的NIR-I和SWIR成像。首次构建了一种多光谱NIR-I / SWIR荧光成像设备,以允许客观地比较两种成像窗口。先在体外对结合物进行了表征。使用以已知几何和材料组成的成像标本评估了NIR-I / SWIR设备的灵敏度和深度穿透性,显示最小可检测体积约为0.9 mm³,深度穿透性可达3 mm。体内,使用NIR-I / SWIR设备进行荧光成像,显示出两种染料的高肿瘤-背景比(TBR),其中抗GD2-IR800比抗GD2-IR12明显更亮。至关重要的是,该系统使SWIR波长的TBR高于NIR-I波长,验证了SWIR成像使肿瘤边缘高对比度分界。通过将抗GD2抗体的高特异性与现有NIR-I染料的可用性和可转化性以及SWIR在深度和肿瘤信号与背景比方面的优势相结合,GD2靶向的NIR-I / SWIR引导手术可以改善神经母细胞瘤患者的治疗,值得在未来的临床试验中进行调查。
Fluorescence-guided surgery is set to play a pivotal role in the intraoperative management of pediatric tumors. Short-wave infrared imaging (SWIR) has advantages over conventional near-infrared I (NIR-I) imaging with reduced tissue scattering and autofluorescence. Here, two NIR-I dyes (IRDye800CW and IR12), with long tails emitting in the SWIR range, were conjugated with a clinical-grade anti-GD2 monoclonal antibody (Dinutuximab-beta) to compare NIR-I and SWIR imaging for neuroblastoma surgery. A first-of-its-kind multispectral NIR-I/SWIR fluorescence imaging device was constructed to allow an objective comparison between the two imaging windows. Conjugates were first characterized in vitro. Tissue-mimicking phantoms, imaging specimens of known geometric and material composition, were used to assess the sensitivity and depth penetration of the NIR-I/SWIR device, showing a minimum detectable volume of ~0.9 mm3 and depth penetration up to 3 mm. In vivo, fluorescence imaging using the NIR-I/SWIR device showed a high tumor-to-background ratio (TBR) for both dyes, with anti-GD2-IR800 being significantly brighter than anti-GD2-IR12. Crucially, the system enabled higher TBR at SWIR wavelengths than at NIR-I wavelengths, verifying SWIR imaging enables high-contrast delineation of tumor margins. This work demonstrates that by combining the high-specificity of anti-GD2 antibodies with the availability and translatability of existing NIR-I dyes, along with the advantages of SWIR in terms of depth and tumor signal-to-background ratio, GD2-targeted NIR-I/SWIR-guided surgery could improve the treatment of neuroblastoma patients, warranting investigation in future clinical trials.