Complete preclinical evaluation of the novel antibody mimetic Nanofitin-IRDye800CW for diverse non-invasive diagnostic applications in the management of HER-2 positive tumors

Abstract There are well-known limitations associated to the use of antibodies in the non-invasive detection of HER-2 expression. In fact, current procedures recommended for diagnostic purposes of HER-2 status are still invasive techniques. Here, a novel, smaller diagnostic probe, the anti-HER-2 Nano...

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Main Authors: Margherita Iaboni, Federico Crivellin, Francesca Arena, Francesca La Cava, Alessia Cordaro, Francesco Stummo, Daniele Faletto, Simon Huet, Leo Candela, Jessy Pedrault, Eugenia R. Zanella, Andrea Bertotti, Francesco Blasi, Alessandro Maiocchi, Luisa Poggi, Erika Reitano
Format: Article
Language:English
Published: Nature Portfolio 2025-03-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-93696-w
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Summary:Abstract There are well-known limitations associated to the use of antibodies in the non-invasive detection of HER-2 expression. In fact, current procedures recommended for diagnostic purposes of HER-2 status are still invasive techniques. Here, a novel, smaller diagnostic probe, the anti-HER-2 Nanofitin conjugated to the fluorophore IRDye800CW (NF-800), underwent an in vitro/in vivo proof of concept study by Optical Imaging. NF-800 showed high affinity and specificity for the cellular target, and the ability to internalize into HER-2 positive cells. By ex vivo analysis, NF-800 showed a selective tumor accumulation in xenograft tumor models, and also a good tumor targeting efficacy in translational preclinical setups, such as orthotopic and patient-derived xenograft (PDX) models. In the latter, NF-800 was compared to the anti-HER-2 antibody Trastuzumab, displaying a large diagnostic advantage. Interestingly, NF-800 did not seem to share the same binding site with Trastuzumab and Pertuzumab, opening specific theragnostic opportunities for NF-800 in combination with standard-of-care antibodies.
ISSN:2045-2322