Intraoperative dual-labeled molecular tracer to improve surgery on neuroblastoma

术中双标记分子示踪剂改善神经母细胞瘤手术

• 批准号: 10737309
• 负责人: Gary Kohanbash
• 金额: $ 59.63万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10737309
• 关键词: Adjuvant Therapy; Adult; Animals; Antibodies; Antigens; Architecture; Cephalic; Characteristics; Childhood; Clinical; Clinical Trials; Complement; Complication; Data; Detection; Development; Discrimination; Disease; Drug Kinetics; Epidermal Growth Factor Receptor; Excision; Exposure to; Eye Surgeon; FDA approved; Face; Family suidae; Fluorescence; Fluorescent Antibody Technique; Goals; Hand; Head and Neck Cancer; Heterogeneity; Human Resources; Image; Imaging Device; Indocyanine Green; Label; Lesion; Location; Malignant Childhood Neoplasm; Manuals; Metastatic Neoplasm to Lymph Nodes; Modality; Modeling; Molecular; Molecular Target; Near-infrared optical imaging; Neoadjuvant Therapy; Nerve; Neuroblastoma; Non-Malignant; Operative Surgical Procedures; Organ; Palpation; Patient-Focused Outcomes; Patients; Pediatric Neoplasm; Pentetic Acid; Performance; Perfusion; Perioperative; Primary Neoplasm; Public Health; Radiation exposure; Radio; Radioisotopes; Rattus; Regional Disease; Research; Rodent; Safety; Sentinel Lymph Node Biopsy; Site; Solid Neoplasm; Structure; Surgeon; Surgical Oncology; Systemic Therapy; Testing; Time; Tissue Model; Tissues; Tracer; Transgenic Mice; Tumor Antigens; Tumor Biology; Tumor Promotion; Visual; Visualization; Work; Xenograft procedure; cancer surgery; high risk; image guided; imaging agent; imaging system; improved; improved outcome; innovation; molecular imaging; mortality; mouse model; near infrared dye; novel; operation; pre-clinical; preservation; radiotracer; success; targeted agent; tool; tumor; tumor specificity; uptake

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.

抽象的。高危神经母细胞瘤 (NB) 的死亡率超过 50%，需要改进治疗，包括 更安全、更完整地切除侵袭性、边界不清的肿瘤及其通常较远、困难的肿瘤 定位淋巴结转移。因此，迫切需要新的术中分子成像（IMI） 能够识别 NB 并帮助保存邻近重要结构的试剂。长期来看 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。本研究的目的是评估一种新型双标记 IMI 示踪剂来指导 NB 识别和安全切除。因此，我们假设双标记 IMI 示踪剂可以针对 术中检测并安全去除NB。第一个目标将集中于优化双标签 IMI 专门用于术中使用的示踪剂。在第二个目标中，将研究肿瘤和组织异质性 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 跟踪器的影响 对有或没有 NB 的转基因小鼠模型和大鼠模型的切除程度和存活率的影响 新辅助治疗和辅助治疗。如果拟议的研究成功，我们的 IMI 追踪器应该允许 外科医生能够更安全、更完整地切除 NB，从而改善患者预后。 NB手术 由于疾病广泛传播，这是小儿外科医生面临的最具挑战性的手术之一 以及肿瘤与正常重要结构之间的密切关系。外科医生面临这些挑战 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。我们提出一个 一种用于特异性检测 NB 的新型双标记分子示踪剂解决了这个问题。这部小说， 术中识别和检测 NB 的实质性不同方法将使 手术，从而为 IMI 药物在小儿癌症手术中的应用开辟了新的视野。