{
  "abstract": "Pretargeting is an emerging strategy for tumor imaging that offers improved specificity and reduced off-target toxicity compared to conventional direct targeting approaches. However, a major limitation lies in the rapid internalization of pretargeting molecules, which reduces the availability of binding sites for effector probes and compromises imaging performance. In this study, we present a GRPR-targeted pretargeting system designed to overcome this challenge by employing the GRPR antagonist peptide RM26, which remains on the cell surface after receptor binding and thus minimizes internalization. The system is based on a bioorthogonal inverse electron-demand Diels-Alder reaction between IBA-RM26-TCO and 99mTc-HYNIC-Tz, which is completed quantitatively within 10 min under physiological conditions, with excellent stability, as evidenced by over 93% radiochemical purity after 24 h. In vitro experiments confirmed that RM26 maintained high GRPR binding affinity with minimal internalization, facilitating robust bioorthogonal reactivity. In vivo SPECT/CT imaging in GRPR-positive U-87MG xenograft mice further demonstrated more than 2-fold higher tumor uptake and an improved tumor-to-muscle ratio compared to direct targeting. Collectively, this work establishes a GRPR antagonist peptide-based pretargeting platform that not only addresses the internalization barrier but also enhances diagnostic performance, offering a safer and more effective approach for precision tumor imaging.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Radiology, The First Affiliated Hospital of Soochow University, State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China.",
    "Institute of Biomedical Engineering, School of Life Sciences, Suzhou Medical College of Soochow University, Suzhou, Jiangsu 215123, China.",
    "Biomedical Basic Research Center (BBRC) of Jiangsu Province, Soochow University, Suzhou, Jiangsu 215123, China.",
    "The Second Affiliated Hospital of Soochow University, Suzhou 215004, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Chaoping Sun"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiuqi Hu"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhongsheng Zhao"
    },
    {
      "affs": [
        0
      ],
      "name": "Yun Gao"
    },
    {
      "affs": [
        0
      ],
      "name": "Mengdan Xu",
      "orcid": "0009-0002-4544-4046"
    },
    {
      "affs": [
        0
      ],
      "name": "Ning Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Qianqian Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Lishu Zhao"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Jianxian Ge",
      "orcid": "0000-0002-4317-1083"
    },
    {
      "affs": [
        0,
        3,
        2
      ],
      "name": "Jianfeng Zeng",
      "orcid": "0000-0001-7654-8724"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fhkqp63avggjr.bib",
  "cited_by": 0,
  "doi": "10.1021/cbmi.6c00069",
  "fulltext_url": "https://europepmc.org/articles/PMC13715353",
  "id": "fhkqp63avggjr",
  "issns": [
    "2832-3637"
  ],
  "landing_url": "https://europepmc.org/article/MED/42953307",
  "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": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "2741|Radiopharmaceutical Chemistry and Applications"
    ]
  ],
  "openalex": "W7163919762",
  "pdf_url": "https://europepmc.org/articles/PMC13715353?pdf=render",
  "pmcid": "PMC13715353",
  "pmid": "42953307",
  "published": "2026-06-08",
  "publisher": "American Chemical Society",
  "ris": "https://research.draconitic.com/paper/fhkqp63avggjr.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T00:20:41Z",
      "native_id": "MED:42953307",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42953307"
    },
    {
      "first_seen": "2026-11-01T12:22:41Z",
      "native_id": "PMC13715353",
      "source": "pmc",
      "url": "https://doi.org/10.1021/cbmi.6c00069"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2741|Radiopharmaceutical Chemistry and Applications",
      "subfield": "imaging"
    }
  ],
  "title": "A GRPR Antagonist Peptide-Based Pretargeting Strategy Overcoming Molecule Internalization for Enhanced Tumor Imaging.",
  "title_text": "A GRPR Antagonist Peptide-Based Pretargeting Strategy Overcoming Molecule Internalization for Enhanced Tumor Imaging.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:22:41Z",
  "url": "https://research.draconitic.com/paper/fhkqp63avggjr",
  "venue": "Chemical & biomedical imaging",
  "versions": []
}