Abstract
Neuroblastoma resection represents a major challenge in pediatric surgery, because of the high risk of complications. Fluorescence-guided surgery (FGS) could lower this risk by facilitating discrimination of tumor from normal tissue and is gaining momentum in adult oncology. Here, we provide the first molecular-targeted fluorescent agent for FGS in pediatric oncology, by developing and preclinically evaluating a GD2-specific tracer consisting of the immunotherapeutic antibody dinutuximab-beta, recently approved for neuroblastoma treatment, conjugated to near-infrared (NIR) fluorescent dye IRDye800CW. We demonstrated specific binding of anti-GD2-IRDye800CW to human neuroblastoma cells in vitro and in vivo using xenograft mouse models. Furthermore, we defined an optimal dose of 1 nmol, an imaging time window of 4 days after administration and show that neoadjuvant treatment with anti-GD2 immunotherapy does not interfere with fluorescence imaging. Importantly, as we observed universal, yet heterogeneous expression of GD2 on neuroblastoma tissue of a wide range of patients, we implemented a xenograft model of patient-derived neuroblastoma organoids with differential GD2 expression and show that even low GD2 expressing tumors still provide an adequate real-time fluorescence signal. Hence, the imaging advancement presented in this study offers an opportunity for improving surgery and potentially survival of a broad group of children with neuroblastoma.
Original language | English |
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Article number | 17667 |
Pages (from-to) | 17667 |
Journal | Scientific Reports |
Volume | 10 |
Issue number | 1 |
DOIs | |
Publication status | Published - 19 Oct 2020 |
Keywords
- Animals
- Benzenesulfonates/therapeutic use
- Brain Neoplasms/metabolism
- Cell Line, Tumor
- Female
- Flow Cytometry
- Fluorescent Dyes/therapeutic use
- Gangliosides/metabolism
- Humans
- Indoles/therapeutic use
- Mice
- Mice, Nude
- Neoplasm Transplantation
- Neoplasms, Experimental
- Neuroblastoma/metabolism
- Tissue Array Analysis