{
  "abstract": "Hepatocellular carcinoma (HCC) remains a major clinical challenge due to its high recurrence rate, poor response to systemic therapies, and unfavorable prognosis. Human epidermal growth factor receptor 3 (HER3) has emerged as a clinically relevant molecular target in HCC. Seribantumab is a fully human IgG2 monoclonal antibody against HER3 and can inhibit downstream pro-survival signaling and exert potential antitumor effects. This study aimed to develop Seribantumab-based HER3-targeted radionuclide drug conjugates (68Ga/177Lu-Seribantumab) for HER3-targeted imaging and radionuclide therapy of HCC. Seribantumab was conjugated with isothiocyanate-benzyl-DOTA and radiolabeled with 68Ga or 177Lu. 177Lu-Seribantumab was evaluated for radiochemical purity, stability, cellular uptake, cytotoxicity, cell-cycle distribution, DNA damage, and apoptosis. PET/CT imaging, biodistribution, therapeutic efficacy, and histology were assessed in HepG2 xenograft mice treated with 68Ga/177Lu-Seribantumab. Both 68Ga-Seribantumab and 177Lu-Seribantumab exhibited high radiochemical purity (>95%) and stability. 177Lu-Seribantumab showed HER3-specific cellular uptake and cytotoxic effects in HepG2 cells. 177Lu-Seribantumab induced G1-phase cell-cycle arrest and enhanced DNA damage and apoptosis (29.1 ± 2.1%) in HepG2 cells, consistent with HER3-targeted effects accompanied by radionuclide-associated cytotoxicity. Similar cell-cycle and apoptotic effects were observed in Huh7 cells. Furthermore, PET/CT showed partly HER3-mediated tumor uptake of 68Ga-Seribantumab, although the tumor-to-liver contrast was modest. SPECT/CT imaging further demonstrated sustained tumor accumulation of 177Lu-Seribantumab in HepG2 xenografts, reaching 1.1 ± 0.1%ID/mL at 24 h, thereby supporting its tumor-targeting capability and therapeutic potential. Histopathological and immunohistochemical analyses revealed extensive tumor necrosis, increased Caspase-3 expression, reduced Ki67 positivity, and decreased HER3-positive tumor cell populations after treatment with radionuclide drug conjugates (RDCs), further supporting the antitumor activity of 177Lu-Seribantumab. 68Ga/177Lu-conjugated Seribantumab enables HER3-targeted molecular imaging and radionuclide therapy in HER3-positive HCC models. These findings support the potential of Seribantumab-based RDCs as a theranostic strategy for HER3-positive HCC.",
  "abstract_shown": true,
  "affiliations": [
    "Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, 201800, People's Republic of China.",
    "Department of Nuclear Medicine, Shanghai Changhai Hospital, Shanghai, 200433, People's Republic of China.",
    "Department of Nuclear Medicine, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Anhui, 230001, People's Republic of China.",
    "Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, People's Republic of China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Jiaojiao Li"
    },
    {
      "affs": [
        1
      ],
      "name": "Xiao Yang"
    },
    {
      "affs": [
        1
      ],
      "name": "Ao Li",
      "orcid": "0009-0002-1857-2288"
    },
    {
      "affs": [
        1
      ],
      "name": "Rou Li"
    },
    {
      "affs": [
        1
      ],
      "name": "Tao Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiaoxu Dong"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Xiao Li"
    },
    {
      "affs": [
        2
      ],
      "name": "Qiang Xie"
    },
    {
      "affs": [
        1
      ],
      "name": "Changjing Zuo"
    },
    {
      "affs": [
        3
      ],
      "name": "Wei Zhang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/d8ef7413awp7j.bib",
  "cited_by": 0,
  "doi": "10.2147/dddt.s646346",
  "fulltext_url": "https://europepmc.org/articles/PMC13715533",
  "id": "d8ef7413awp7j",
  "issns": [
    "1177-8881"
  ],
  "landing_url": "https://europepmc.org/article/MED/42953395",
  "language": "eng",
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Research"
    ],
    [
      "openalex",
      "2741|Radiopharmaceutical Chemistry and Applications"
    ]
  ],
  "openalex": "W7223408040",
  "pdf_url": "https://europepmc.org/articles/PMC13715533?pdf=render",
  "pmcid": "PMC13715533",
  "pmid": "42953395",
  "published": "2026-10-24",
  "publisher": "Dove Press",
  "ris": "https://research.draconitic.com/paper/d8ef7413awp7j.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T00:20:40Z",
      "native_id": "MED:42953395",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42953395"
    },
    {
      "first_seen": "2026-11-01T12:22:48Z",
      "native_id": "PMC13715533",
      "source": "pmc",
      "url": "https://doi.org/10.2147/dddt.s646346"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2741|Radiopharmaceutical Chemistry and Applications",
      "subfield": "imaging"
    }
  ],
  "title": "⁶⁸Ga/¹⁷⁷Lu-Labeled Seribantumab as the Theranostic Drugs in Treating HER3-Positive Hepatocellular Carcinoma.",
  "title_text": "⁶⁸Ga/¹⁷⁷Lu-Labeled Seribantumab as the Theranostic Drugs in Treating HER3-Positive Hepatocellular Carcinoma.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:22:48Z",
  "url": "https://research.draconitic.com/paper/d8ef7413awp7j",
  "venue": "Drug design, development and therapy",
  "versions": []
}