{
  "abstract": "Background\n\nOverexpression of fibroblast activation protein (FAP) in cancer-associated fibroblasts enables a highly selective targeting strategy using FAP inhibitors. However, radiolabeled small-molecule FAP inhibitors (FAPIs) show limited tumor retention, restricting therapeutic applications. Multimerization represents a promising strategy to enhance tumor uptake and retention through polyvalent binding. Here, we report the rational design and evaluation of dimeric FAP-targeted radiopharmaceuticals for theranostic applications.Results\n\nBased on the (4-quinolinoyl)-glycyl-2-cyanopyrrolidine (QCP) scaffold, a series of monomeric FAPIs were assembled into dimeric radioligands using three distinct tripod-based platforms and equipped with a DOTA-GA chelator for efficient radiolabeling with indium-111 and lutetium-177; systematic in vitro and in vivo evaluation of binding affinity, stability, cellular uptake, and tumor targeting identified eFAP-51 and eFAP-52 as lead candidates, both showing high radiochemical yield and purity, favorable stability, and sub-nanomolar affinity for FAP with strong selectivity over DPP4. Further studies demonstrated superior tumor targeting and pharmacokinetics for eFAP-51 compared with the clinical reference FAPI-46, with [¹¹¹In]In-eFAP-51 exhibiting more than 4-fold higher tumor uptake at 48 h post-injection (3.2 ± 0.5 vs. 0.71 ± 0.1%ID/g) and prolonged retention. eFAP-51 was subsequently radiolabeled with lutetium-177 to yield a stable therapeutic candidate, and dose-dependent studies revealed that intermediate molar doses (0.3-0.6 nmol) provided an optimal balance between tumor uptake and tumor-to-background contrast.Conclusions\n\nThe FAPI dimer eFAP-51 showed favorable tumor targeting and pharmacokinetics, supporting its potential for clinical translation in theranostic oncology.",
  "abstract_shown": true,
  "affiliations": [
    "Erasmus MC, Department of Radiology and Nuclear Medicine, University Medical Center Rotterdam, Rotterdam, The Netherlands.",
    "Erasmus MC Cancer Institute, Rotterdam, The Netherlands.",
    "Erasmus MC, Department of Radiology and Nuclear Medicine, University Medical Center Rotterdam, Rotterdam, The Netherlands. y.seimbille@erasmusmc.nl.",
    "Erasmus MC Cancer Institute, Rotterdam, The Netherlands. y.seimbille@erasmusmc.nl."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Le Li",
      "orcid": "0009-0006-4306-5359"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Hanyue Ma"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Amber Piet"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Corrina de Ridder"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Debra Stuurman"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Priciana Paraïso"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Yann Seimbille"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3rec4662rtsx8.bib",
  "cited_by": 0,
  "doi": "10.1186/s41181-026-00481-9",
  "fulltext_url": "https://europepmc.org/articles/PMC13680315",
  "id": "3rec4662rtsx8",
  "issns": [
    "2365-421X"
  ],
  "landing_url": "https://europepmc.org/article/MED/42897329",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "R895-920"
    ],
    [
      "lcc",
      "RM1-950"
    ],
    [
      "openalex",
      "2741|Radiopharmaceutical Chemistry and Applications"
    ]
  ],
  "openalex": "W7170336502",
  "pdf_url": "https://europepmc.org/articles/PMC13680315?pdf=render",
  "pmcid": "PMC13680315",
  "pmid": "42897329",
  "published": "2026-07-01",
  "publisher": "SpringerOpen",
  "ris": "https://research.draconitic.com/paper/3rec4662rtsx8.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:41Z",
      "native_id": "MED:42897329",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42897329"
    },
    {
      "first_seen": "2026-10-30T13:46:33Z",
      "native_id": "6cae06d180f04aeb8ba94a94830109cb",
      "source": "doaj",
      "url": "https://doi.org/10.1186/s41181-026-00481-9"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2741|Radiopharmaceutical Chemistry and Applications",
      "subfield": "imaging"
    }
  ],
  "title": "eFAP-51, a novel FAPI dimer with enhanced tumor uptake and retention for theranostic applications.",
  "title_text": "eFAP-51, a novel FAPI dimer with enhanced tumor uptake and retention for theranostic applications.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:46:33Z",
  "url": "https://research.draconitic.com/paper/3rec4662rtsx8",
  "venue": "EJNMMI radiopharmacy and chemistry",
  "versions": []
}