An Imaging Study of Anti-GD2-800CW in Patients With Neuroblastoma

Neuroblastoma is the most commonly diagnosed extracranial solid tumor in young children. It is a neural crest derived malignancy, which are the cells that give rise to the sympathetic nervous system, and can therefore be located in different body compartments. However, it occurs most frequently (80%) in the abdomen. Current treatment involves debulking surgery using standard-of-care, not assisted by intra-operative visualization of the tumor. In this current situation there is, i) a high risk of severe complications such as bleeding or unplanned nephrectomy (40%), ii) a high chance of \>10% residual tumor tissue, and iii) difficulty distinguishing neuroblastoma subtypes with varying malignancy. Therefore, there is a high need for new tools enabling tumor-specific intra-operative visualization to assist the surgeon. This will reduce surgical complications and ensure neuroblastoma cells can be visualized and resected during surgery. Over the past years, Fluorescence Guided Surgery (FGS) has proven to be a useful intraoperative tool to increase the visibility of the tumor in various adult cancers. Our group has developed and validated a tumor-specific fluorescent agent, anti-GD2-800CW, that can be used to visualize neuroblastoma during surgery. Anti-GD2-800CW consists of two substances. Firstly, the monoclonal antibody anti-GD2, also known as Qarziba or Dinutuximab-beta, which binds to Disialoganglioside 2 (GD2), a tumor-associated antigen specifically expressed by neuroblastoma, most melanomas and several other tumors. Immunotherapy with anti-GD2 is now standard therapy for high-risk neuroblastoma treatment in patients aged 12 months and above. Secondly, the near-infrared (NIR) fluorescent dye, IRDye800CW, which is used extensively in clinical trials as fluorescent imaging agent without any known adverse events (AEs). The aim of this study is to investigate the safety and efficacy of this novel agent, anti-GD2-800CW, to visualize neuroblastoma during surgery.

• To assess the pharmacodynamic characteristics of an i.v. injection of anti-GD2-800CW. [Срок оценки: From just before infusion to 4 days after surgery.]
• To assess the pharmacokinetic characteristics of an i.v. injection of anti-GD2-800CW. [Срок оценки: From just before infusion to 4 days after surgery.]
• To correlate clinical imaging data with histopathology data to determine the accuracy for depicting GD-2 expressing vital tumor cells. [Срок оценки: From start surgery to 3 weeks after surgery when the PA results are analyzed.]
• To assess the intra-operative usability of anti-GD2-800CW to distinguish tumor tissue from surrounding tissue on eyesight of the surgeons. [Срок оценки: From start surgery to 3 weeks after surgery when the PA results are analyzed.]
• To assess whether tumor load influences the fluorescence intensity. [Срок оценки: From pre-operative scan to when PA results are analyzed, 3 weeks after surgery.]