Anti-GD2-IRDye800CW as a targeted probe for fluorescence-guided surgery in neuroblastoma

Lianne M Wellens, Marion M Deken, Cornelis F M Sier, Hannah R 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

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)

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 languageEnglish
Article number17667
Pages (from-to)17667
JournalScientific Reports
Volume10
Issue number1
DOIs
Publication statusPublished - 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

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