{
  "abstract": "Despite the increasing clinical adoption of molecular fluorescence-guided surgery (FGS), the limited tumour specificity of currently available contrast agents remains a challenge for accurate tumour identification. This study aimed to validate a single-domain antibody (sdAb)-based tracer specifically targeting the human folate receptor alpha (hFRα) and evaluate its specificity and in vivo pharmacokinetics compared to an established folate receptor targeted tracer. The anti-hFRα sdAb 2BD42 was conjugated to the near-infrared dye s775z. Following quality control, in vitro studies assessed binding specificity towards hFRα and hFRβ. Subsequently, its longitudinal in vivo biodistribution profile in a subcutaneous xenograft model was compared to that of OTL-38. Finally, the applicability of sdAb 2BD42-s775z was evaluated as a proof-of-concept in ovarian carcinomatosis and orthotopic lung tumour models. Following successful fluorescence labelling, sdAb 2BD42-s775z retained sub-nanomolar affinity for hFRα and selectively discriminated hFRα from hFRβ in vitro, in contrast to OTL-38. Furthermore, sdAb 2BD42-s775z exhibited a rapid tumour accumulation and a relevant tumour-to-background ratio (TBR) of 4.1 ± 0.9 at 1 h post-injection which persisted for up to 1 week post-injection, while for OTL-38, a relevant TBR was developed more slowly from 24 h post-injection onwards. In addition, sdAb 2BD42-s775z was able to rapidly and specifically highlight tumour lesions in an ovarian carcinomatosis and orthotopic lung tumour model, whereas no tumour uptake was observed with an irrelevant sdAb. To conclude, 2BD42-s775z demonstrated high specificity for hFRα, favourable TBR contrast, and rapid tumour visualisation in preclinical ovarian and lung cancer models, highlighting its potential for FGS. Further studies are warranted to determine whether selective hFRα targeting improves the detection of lymph node metastases compared with currently available folate receptor-targeted tracers.",
  "abstract_shown": true,
  "affiliations": [
    "Molecular Imaging and Therapy Research Group (MITH), Faculty of Medicine and Pharmacy, Brussels Health Campus, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels, Belgium",
    "Precirix NV, 1090 Brussels, Belgium",
    "Institute for Drug Discovery, Purdue University, West Lafayette, IN 47907, USA"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Sam Floru",
      "orcid": "0000-0002-2385-5947"
    },
    {
      "affs": [
        0
      ],
      "name": "Stijn Vandorpe"
    },
    {
      "affs": [
        1
      ],
      "name": "Laurent Navarro",
      "orcid": "0009-0009-8021-5346"
    },
    {
      "affs": [
        2
      ],
      "name": "Shivakrishna Kallepu"
    },
    {
      "affs": [
        2
      ],
      "name": "Madduri Srinivasarao",
      "orcid": "0000-0003-3056-4571"
    },
    {
      "affs": [
        2
      ],
      "name": "Philip Stewart Low",
      "orcid": "0000-0001-9042-5528"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Matthias D’Huyvetter"
    },
    {
      "affs": [
        0
      ],
      "name": "Sophie Hernot",
      "orcid": "0000-0002-8739-6137"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8b23advf7gjrs.bib",
  "cited_by": 0,
  "doi": "10.3390/biom16101426",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13702722/?tool=EBI",
  "id": "8b23advf7gjrs",
  "issns": [
    "2218-273X"
  ],
  "landing_url": "https://www.mdpi.com/2218-273X/16/10/1426",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2741|Radiopharmaceutical Chemistry and Applications"
    ]
  ],
  "openalex": "W7215090351",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13702722/pdf/?tool=EBI",
  "pmcid": "PMC13702722",
  "pmid": null,
  "published": "2026-10-01",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/8b23advf7gjrs.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:59Z",
      "native_id": "10.3390/biom16101426",
      "source": "crossref",
      "url": "https://www.mdpi.com/2218-273X/16/10/1426"
    },
    {
      "first_seen": "2026-10-30T12:21:34Z",
      "native_id": "PMC:PMC13702722",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13702722"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2741|Radiopharmaceutical Chemistry and Applications",
      "subfield": "imaging"
    }
  ],
  "title": "Validation of a Highly Specific Anti-Human Folate Receptor Alpha Single-Domain Antibody for Rapid Fluorescence-Guided Surgery of Ovarian and Lung Cancer",
  "title_text": "Validation of a Highly Specific Anti-Human Folate Receptor Alpha Single-Domain Antibody for Rapid Fluorescence-Guided Surgery of Ovarian and Lung Cancer",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:21:34Z",
  "url": "https://research.draconitic.com/paper/8b23advf7gjrs",
  "venue": "Biomolecules",
  "versions": []
}