Anti-GD2-IRDye800CW as a targeted probe for fluorescence-guided surgery in neuroblastoma
Lianne M. Wellens, Marion M. Deken, Cornelis F.M. Sier, Hannah Johnson, Fàtima de la Jara Ortiz, Shadhvi S. Bhairosingh, Ruben D. Houvast, Waleed M. Kholosy, Victor M. Baart, Annique M. M. J. Pieters, Ronald R. de Krijger, Jan J. Molenaar, Ellen J. Wehrens, Johanna F. Dekkers, Marc H. W. A. Wijnen, Alexander L. Vahrmeijer, Anne C. Rios
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.