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<p>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&#xa0;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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年3月21日

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  • 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

摘要

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.