Journal Article

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

Pedrault, Jessy, Poggi, Luisa, Faletto, Daniele, Stummo, Francesco, Maiocchi, Alessandro, La Cava, Francesca, Cordaro, Alessia, Arena, Francesca, Candela, Leo, Bertotti, Andrea, Blasi, Francesco, Crivellin, Federico, Zanella, Eugenia R., Reitano, Erika, Iaboni, Margherita, Huet, Simon

2025

Overview

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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 631/1647/245 / 631/67/1857 / 631/67/2321 / Animals / Antibodies / Antibodies, Monoclonal, Humanized / Binding sites / Biodistribution / Cell Line, Tumor / ErbB-2 protein / Female / Fluorescent Dyes - chemistry / Gene amplification / HER-2 / Humanities and Social Sciences / Humans / Kinases / Mice / Monoclonal antibodies / multidisciplinary / Nanofitin / Near-infrared / Neoplasms - diagnosis / Neoplasms - metabolism / Optical imaging / Optical Imaging - methods / Proteins / Receptor, ErbB-2 - metabolism / Ribonucleic acid / RNA / Science / Science (multidisciplinary) / Trastuzumab / Trastuzumab - pharmacology / Tumors / Xenograft Model Antitumor Assays / Xenografts