Short-wave infrared imaging enables high-contrast fluorescence-guided surgery in neuroblastoma

Laura Privitera, Dale J. Waterhouse, Alessandra Preziosi, Irene Paraboschi, Olumide Ogunlade, Chiara Da Pieve, Marta Barisa, Olumide Ogunbiyi, Gregory Weitsman, J. Ciaran Hutchinson, Kate Cross, Lorenzo Biassoni, Danail Stoyanov, Neil Sebire, Paul Beard, Paolo De Coppi, Gabriela Kramer-Marek, Stefano Giuliani*, John T Anderson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Fluorescence-guided surgery is set to play a pivotal role in the intraoperative management of pediatric tumors. Short-wave infrared imaging (SWIR) has advantages over conventional near-infrared I (NIR-I) imaging with reduced tissue scattering and autofluorescence. Here, two NIR-I dyes (IRDye800CW and IR12), with long tails emitting in the SWIR range, were conjugated with a clinical-grade anti-GD2 monoclonal antibody (Dinutuximab-beta) to compare NIR-I and SWIR imaging for neuroblastoma surgery. A first-of-its-kind multispectral NIR-I/SWIR fluorescence imaging device was constructed to allow an objective comparison between the two imaging windows. Conjugates were first characterized in vitro. Tissue-mimicking phantoms, imaging specimens of known geometric and material composition, were used to assess the sensitivity and depth penetration of the NIR-I/SWIR device, showing a minimum detectable volume of ~0.9 mm3 and depth penetration up to 3 mm. In vivo, fluorescence imaging using the NIR-I/SWIR device showed a high tumor-to-background ratio (TBR) for both dyes, with anti-GD2-IR800 being significantly brighter than anti-GD2-IR12. Crucially, the system enabled higher TBR at SWIR wavelengths than at NIR-I wavelengths, verifying SWIR imaging enables high-contrast delineation of tumor margins. This work demonstrates that by combining the high-specificity of anti-GD2 antibodies with the availability and translatability of existing NIR-I dyes, along with the advantages of SWIR in terms of depth and tumor signal-to-background ratio, GD2-targeted NIR-I/SWIR-guided surgery could improve the treatment of neuroblastoma patients, warranting investigation in future clinical trials.
Original languageEnglish
JournalCancer Research
Early online date19 Mar 2023
DOIs
Publication statusE-pub ahead of print - 19 Mar 2023

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