{
  "abstract": "Rationale: Poly(ADP-ribose) polymerase-1 (PARP1) is a central mediator of DNA damage response and is upregulated in glioma, supporting it as a molecular imaging biomarker. However, quantitative PET assessment of PARP1 in infiltrative tumors with a preserved blood-brain barrier remains an unmet need. In this study, we evaluated if [18F]Itareparib, a brain-penetrant, non-trapping, PARP1-selective radioligand with reversible kinetics, could improve brain tumor diagnosis and enable target occupancy studies in neurooncology. Methods: [18F]Itareparib was synthesized and evaluated in an orthotopic rat model of BT142 IDH1-mutant gliomas. Dynamic PET scans were performed with or without the administration of the PARP1-selective inhibitor AZD9574. Standardized uptake value ratios (SUVRs) for tumors were calculated using the contralateral region as reference and compared with distribution volume ratios (DVRs) calculated using kinetic modeling. PARP1-specific binding and tracer stability were assessed using autoradiography, immunofluorescence, biodistribution, and radiometabolite analysis. Brain kinetics of [18F]Itareparib were evaluated in a healthy nonhuman primate (NHP) at baseline and blocking conditions. Results: [18F]Itareparib rapidly entered the rat brains and showed 4-fold higher uptake in BT142 tumors than in the contralateral brain. AZD9574 reduced tumor uptake by 77%, supporting the PARP1-specific binding of [18F]Itareparib in the tumors. SUVR(30-60 min) showed the closest agreement with DVR. Autoradiographic tumor-to-reference mean ratio was 7.3, and AZD9574 reduced the tumor-to-reference ratio by 56%. PARP1 immunofluorescence was higher in tumor than the rest of the brain and correlated with autoradiographic results. In rats, the parent fraction of [18F]Itareparib exceeded 99% in brain through 60 min post tracer injection (p.i.) and was approximately 88% in plasma at 60 min p.i. In the NHP, [18F]Itareparib showed rapid brain uptake, and VT decreased by 21+/-6 % after blocking with AZD9574. Conclusion: [18F]Itareparib showed brain penetration, high in vivo metabolic stability, reversible binding kinetics, and PARP1-specific tumor uptake. These findings support further development of [18F]Itareparib for the quantitative PET imaging of PARP1 in brain tumors.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 17,
  "authors": [
    {
      "name": "Peng Wen Tan"
    },
    {
      "name": "Nira Hernandez-Martin"
    },
    {
      "name": "Claudia Esposito-Zapero"
    },
    {
      "name": "Christina Sun"
    },
    {
      "name": "Takuya Toyonaga"
    },
    {
      "name": "Ming-Ǫiang Zheng"
    },
    {
      "name": "Michael Kapinos"
    },
    {
      "name": "Monique A Thomas"
    },
    {
      "name": "Syed Faraz Nejati"
    },
    {
      "name": "Clement Korsah"
    },
    {
      "name": "Daniel Holden"
    },
    {
      "name": "Baosheng Chen"
    },
    {
      "name": "Jorge Sepulcre"
    },
    {
      "name": "Richard E. Carson"
    },
    {
      "name": "Yiyun Huang"
    },
    {
      "name": "Henk M. De Feyter"
    },
    {
      "name": "Zhengxin Cai",
      "orcid": "0000-0002-2005-6760"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7df9jyxwjmy1n.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.16.758050",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.16.758050v1.full",
  "id": "7df9jyxwjmy1n",
  "issns": [
    "2692-8205"
  ],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.16.758050v1",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "cancer biology"
    ],
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "2741|Radiopharmaceutical Chemistry and Applications"
    ]
  ],
  "openalex": "W7222982377",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.16.758050v1.full.pdf",
  "pmcid": "PMC13738528",
  "pmid": "42995898",
  "published": "2026-10-16",
  "publisher": "Cold Spring Harbor Laboratory Preprints",
  "ris": "https://research.draconitic.com/paper/7df9jyxwjmy1n.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:28:32Z",
      "native_id": "10.64898/2026.10.16.758050",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.16.758050v1"
    },
    {
      "first_seen": "2026-11-09T12:23:29Z",
      "native_id": "PMC13738528",
      "source": "pmc",
      "url": "https://doi.org/10.64898/2026.10.16.758050"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:cancer biology",
      "subfield": "oncology"
    }
  ],
  "title": "Preclinical Evaluation of Itareparib, a brain penetrant PARP1-selective radioligand, in Glioma Rat Model and Nonhuman Primate",
  "title_text": "Preclinical Evaluation of Itareparib, a brain penetrant PARP1-selective radioligand, in Glioma Rat Model and Nonhuman Primate",
  "type": "preprint",
  "updated_at": "2026-11-09T12:23:29Z",
  "url": "https://research.draconitic.com/paper/7df9jyxwjmy1n",
  "venue": "bioRxiv",
  "versions": []
}