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: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-03-01
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| Series: | Scientific Reports |
| Subjects: | |
| 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. |
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| ISSN: | 2045-2322 |