Shortwave Infrared Imaging Enables High-Contrast Fluorescence-Guided Surgery in Neuroblastoma.
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Embargo End Date
ICR Authors
Authors
Privitera, L
Waterhouse, DJ
Preziosi, A
Paraboschi, I
Ogunlade, O
Da Pieve, C
Barisa, M
Ogunbiyi, O
Weitsman, G
Hutchinson, JC
Cross, K
Biassoni, L
Stoyanov, D
Sebire, N
Beard, P
De Coppi, P
Kramer-Marek, G
Anderson, J
Giuliani, S
Waterhouse, DJ
Preziosi, A
Paraboschi, I
Ogunlade, O
Da Pieve, C
Barisa, M
Ogunbiyi, O
Weitsman, G
Hutchinson, JC
Cross, K
Biassoni, L
Stoyanov, D
Sebire, N
Beard, P
De Coppi, P
Kramer-Marek, G
Anderson, J
Giuliani, S
Document Type
Journal Article
Date
2023-06-15
Date Accepted
2023-03-08
Abstract
UNLABELLED: Fluorescence-guided surgery is set to play a pivotal role in the intraoperative management of pediatric tumors. Shortwave 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 patients with neuroblastoma, warranting investigation in future clinical trials. SIGNIFICANCE: Multispectral near-infrared I/shortwave infrared fluorescence imaging is a versatile system enabling high tumor-to-background signal for safer and more complete resection of pediatric tumors during surgery.
Citation
Cancer Research, 2023, pp. CAN-22-2918 -
Source Title
Cancer Research
Publisher
AMER ASSOC CANCER RESEARCH
ISSN
0008-5472
eISSN
1538-7445
1538-7445
1538-7445
Collections
Research Team
Preclin Molecular Imaging