{
  "abstract": "BackgroundTriple-negative breast cancer (TNBC) has limited targeted treatment options and is strongly influenced by stromal biology. This study evaluated [177Lu]Lu-FAPI for fibroblast activation protein-alpha (FAP)-directed tumor microenvironment targeting in TNBC models.Methods[177Lu]Lu-FAPI was assessed using TNBC stromal FAP analysis, radiochemical quality control, in vitro stability, cellular uptake and blocking assays, internalization and retention studies, serial biodistribution, Single-photon emission computed tomography/computed tomography (SPECT/CT), autoradiography, Medical Internal Radiation Dose (MIRD)-based dosimetry, and preliminary systemic and histologic safety evaluation. The DOTA-FAPI-04 precursor (FAPI-4; CAS 2374782-02-0; molecular formula C40H54F2N10O10; molecular weight, 872.92 g/mol) was obtained from a commercial supplier (MedChemExpress, Shanghai, China, Cat. No. HY-130196) with confirmed purity ≥95% via high-performance liquid chromatography (HPLC).ResultsTNBC stroma showed prominent FAP expression with α-SMA co-localization. [177Lu]Lu-FAPI showed radiochemical purity of 98.7% ± 0.8% via radio-HPLC and 96.1% ± 1.2% via radio-thin-layer chromatography (radio-TLC). At 72 h, intact tracer remained at 92.1% ± 2.7% in saline and 83.4% ± 2.9% in serum. Competitive binding assays revealed an IC50 of 12.3 ± 2.1 nM and a Ki of 8.7 ± 1.5 nM for FAP. FAP-positive cancer-associated fibroblast (CAF)-like cells showed blocking-sensitive uptake, progressive internalization, and prolonged retention. Tumor uptake persisted through 72 h, while blood activity declined to 0.02%ID/g. SPECT/CT and autoradiography confirmed FAP-associated tumor localization. Revised dosimetry estimated absorbed dose as 0.73 ± 0.15 mGy/MBq for tumor and 4.83 ± 0.52 mGy/MBq for the kidney. The tumor-to-kidney absorbed-dose ratio was 0.15, confirming the kidney as the primary organ-at-risk consideration.Conclusions[177Lu]Lu-FAPI showed stromal-targeted TNBC localization and feasible preclinical dosimetry, with the kidney remaining the main organ-at-risk consideration. These findings establish the pharmacokinetic and dosimetric foundation for [177Lu]Lu-FAPI in TNBC; however, therapeutic efficacy remains to be demonstrated in future studies.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "Original Research",
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "name": "Zhihua Tang"
    },
    {
      "name": "Lushan Yu"
    },
    {
      "name": "Ke Zhang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7r8m9jwztgz8f.bib",
  "cited_by": 0,
  "doi": "10.3389/fonc.2026.1958236",
  "fulltext_url": null,
  "id": "7r8m9jwztgz8f",
  "issns": [
    "2234-943X"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fonc.2026.1958236",
  "language": null,
  "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": [
    [
      "feed-journal",
      "medicine/oncology"
    ]
  ],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-04",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/7r8m9jwztgz8f.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T06:20:42Z",
      "native_id": "10.3389/fonc.2026.1958236",
      "source": "feed-frontiers",
      "url": "https://www.frontiersin.org/articles/10.3389/fonc.2026.1958236"
    },
    {
      "first_seen": "2026-11-04T12:21:46Z",
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      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fonc.2026.1958236/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "feed-journal:medicine/oncology",
      "subfield": "oncology"
    }
  ],
  "title": "Pharmacokinetic and dosimetric evaluation of [177Lu]Lu-FAPI for stromal-targeted radionuclide therapy in triple-negative breast cancer: a preclinical biodistribution and dosimetry study",
  "title_text": "Pharmacokinetic and dosimetric evaluation of [177Lu]Lu-FAPI for stromal-targeted radionuclide therapy in triple-negative breast cancer: a preclinical biodistribution and dosimetry study",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T00:21:26Z",
  "url": "https://research.draconitic.com/paper/7r8m9jwztgz8f",
  "venue": "Frontiers in Oncology",
  "versions": []
}