Intraoperative dual-labeled molecular tracer to improve surgery on neuroblastoma

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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.