Hennessy Megan, Neville Jonathan J, Privitera Laura, Sedgwick Adam, Anderson John, Giuliani Stefano
Cancer Section, Developmental Biology and Cancer Programme, UCL Great Ormond Street Institute of Child Health, London WC1N 1EH, UK.
Royal Free Hospital NHS Foundation Trust, London NW3 2QG, UK.
Children (Basel). 2025 Apr 24;12(5):550. doi: 10.3390/children12050550.
: Targeted and non-targeted fluorescent molecular probes (FMPs) can be used intra-operatively to visualise tumour tissue. Multiple probes have been clinically approved for fluorescence-guided surgery (FGS) in adult oncology, and the translation of these technologies to paediatric neuroblastoma may provide novel strategies for optimising tumour resection whilst minimising morbidity. We aimed to identify clinically approved FMPs with potential utility for FGS in neuroblastoma. : A systematic review of the literature was performed in accordance with the PRISMA guidelines (PROSPERO CRD42024541623). PubMed and Web of Science databases were searched to identify studies investigating clinically approved FGS probes and/or their targets in the context of neuroblastoma. Pre-clinical and clinical studies looking at human neuroblastoma were included. The primary outcomes were that the FGS probe was tested in patients with neuroblastoma, the probe selectively accumulated in neuroblastoma tissue, or that the target of the probe was selectively over-expressed in neuroblastoma tissue. : Forty-two studies were included. Four were clinical studies, and the remainder were pre-clinical studies using human neuroblastoma cell lines, human tumour tissue, or xenograft models using human neuroblastoma cells. The only FMP clinically evaluated in neuroblastoma is indocyanine green (ICG). FMP targets that have been investigated in neuroblastoma include poly-ADP ribose polymerase (PARP) (targeted by PARPiFL), endothelial growth factor receptor (EGFR) (targeted by Panitumumab-IRDye800CW, Cetuximab-IRDye800CW, Nimotuzumab-IRDye800CW and QRHKPRE-Cy5), vascular endothelial growth factor receptor (VEGFR) (targeted by Bevacizumab IRDye800CW), and proteases such as cathepsins and matrix metalloproteinases that activate the fluorescent signal of FMPs, such as LUM015 and AVB-620. Of the clinical studies included, all were found to have a high risk of bias. : ICG is the only clinically approved fluorescent dye currently used for FGS in neuroblastoma; however, studies suggest that its ability to recognise neuroblastoma tissue is inconsistent. There are several clinically approved FMPs, or FMPs in clinical trials, that are used in adult oncology surgery that have targets expressed in neuroblastoma. Further research should validate these probes in neuroblastoma to enable their rapid translation into clinical practice.
靶向和非靶向荧光分子探针（FMPs）可在手术中用于可视化肿瘤组织。多种探针已在成人肿瘤学中获得临床批准用于荧光引导手术（FGS），将这些技术转化应用于儿童神经母细胞瘤可能为优化肿瘤切除同时将发病率降至最低提供新策略。我们旨在确定对神经母细胞瘤FGS具有潜在实用价值的临床批准FMPs。
按照PRISMA指南（PROSPERO CRD42024541623）对文献进行系统综述。检索PubMed和Web of Science数据库，以识别在神经母细胞瘤背景下研究临床批准的FGS探针和/或其靶点的研究。纳入观察人类神经母细胞瘤的临床前和临床研究。主要结果是FGS探针在神经母细胞瘤患者中进行了测试，探针在神经母细胞瘤组织中选择性积聚，或者探针的靶点在神经母细胞瘤组织中选择性过表达。
纳入42项研究。4项为临床研究，其余为使用人类神经母细胞瘤细胞系、人类肿瘤组织或人类神经母细胞瘤细胞异种移植模型的临床前研究。在神经母细胞瘤中进行临床评估的唯一FMP是吲哚菁绿（ICG）。在神经母细胞瘤中研究过的FMP靶点包括聚ADP核糖聚合酶（PARP）（由PARPiFL靶向）、内皮生长因子受体（EGFR）（由帕尼单抗 - IRDye800CW、西妥昔单抗 - IRDye800CW、尼妥珠单抗 - IRDye800CW和QRHKPRE - Cy5靶向）、血管内皮生长因子受体（VEGFR）（由贝伐单抗IRDye800CW靶向）以及诸如组织蛋白酶和基质金属蛋白酶等蛋白酶，它们可激活FMPs（如LUM015和AVB - 620）的荧光信号。在所纳入的临床研究中，均发现存在高偏倚风险。
ICG是目前唯一在神经母细胞瘤FGS中临床批准使用的荧光染料；然而，研究表明其识别神经母细胞瘤组织的能力并不一致。有几种在成人肿瘤手术中使用的临床批准的FMPs或处于临床试验阶段的FMPs，其靶点在神经母细胞瘤中表达。进一步研究应在神经母细胞瘤中验证这些探针，以便能迅速将其转化为临床实践。
