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

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

Samenvatting

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.

Originele taal-2Engels
Pagina's (van-tot)17667
TijdschriftScientific Reports
Volume10
Nummer van het tijdschrift1
DOI's
StatusGepubliceerd - 19 okt. 2020

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