Intraoperative dual-labeled molecular tracer to improve surgery on neuroblastoma

抽象的。由于死亡率超过50%，高危神经母细胞瘤(NB)需要改进治疗，包括 更安全、更彻底地切除侵袭性、边界较差的肿瘤及其往往遥远、困难的肿瘤 以确定淋巴结转移的位置。因此，迫切需要新的术中分子成像(Imi)。 将允许识别NB并帮助保存邻近重要结构的试剂。长期的 我们研究的目标是开发一种用于NB(和其他肿瘤)的IMI示踪剂，以改善结果和 手术切除的安全性。本研究的目的是评价一种新型的、双标记的IMI示踪剂来指导NB 辨认和安全切除。因此，我们假设双标记IMI示踪剂可以被优化用于 术中检测和安全取出NB。第一个目标将集中在优化双标记IMI 特定术中使用的示踪剂。第二个目标是研究肿瘤和组织的异质性 确定它们对IMI示踪剂性能的影响。在最终目标中，我们将评估IMI示踪剂的影响 Nb转基因小鼠模型和大鼠Nb模型切除和存活范围的研究 新辅助和辅助治疗。如果拟议的研究成功，我们的IMI示踪剂应该可以 外科医生可以更安全、更彻底地切除NB，从而改善患者的预后。NB手术 是儿科外科医生面临的最具挑战性的手术之一，因为疾病的广泛传播 以及肿瘤与正常的重要结构之间的密切关系。外科医生面临着这些挑战 今天，他们使用了一个多世纪以来使用的相同工具，可视化和手动触诊。我们提出了一个 这一问题的新解决方案是一种新的双标记分子示踪剂，用于特定的Nb检测。这部小说， 术中识别和检测NB的本质不同的方法将使更有效 因此，IMI制剂在儿科癌症手术中的应用开辟了新的天地。

Abstract. With a mortality rate of over 50%, high-risk neuroblastoma (NB) requires improved therapy, including safer and more complete resection of aggressive, poorly circumscribed tumors and their often remote, difficult to locate lymph node metastases. Thus, there is a critical need for new intraoperative molecular imaging (IMI) agents that will allow identification of NB and aid in preservation of adjacent vital structures. The long-term goal of our research is to develop an IMI tracer for use in NB (and other tumors) to improve the outcomes and safety of surgical resection. The objective of this study is to evaluate a novel, dual-labeled IMI tracer to guide NB identification and safe resection. We therefore hypothesize that a dual-labeled IMI tracer can be optimized for intraoperative detection and safe removal of NB. The first aim will focus on optimizing a dual-labeled IMI tracer specifically for intraoperative use. In the second aim, tumor and tissue heterogeneity will be studied to determine their effects on IMI tracer performance. In the final aim, we will evaluate the impact of the IMI tracer on extent of resection and survival in a transgenic mouse model and a rat model of NB with or without neoadjuvant and adjuvant therapies. If successful with the proposed studies, our IMI tracer should allow surgeons to perform safer and more complete resection of NB, leading to improved patient outcomes. NB surgery is among the most challenging operations to confront the pediatric surgeon due to extensive spread of disease and the intimate relationship between the tumor and normal, vital structures. The surgeon faces these challenges today with the same tools they have used for over a century, visualization and manual palpation. We propose a new solution to this problem with a novel dual-labeled molecular tracer for specific detection of NB. This novel, substantively different approach to intraoperative identification and detection of NB will enable more efficacious surgery, thereby opening new horizons in the application of IMI agents for pediatric cancer surgery.