{
  "abstract": "Background\n\nThe androgen receptor (AR) is upregulated in multiple cancers, such as salivary gland cancer, glioblastoma, triple-negative breast cancer, and, most commonly, prostate cancer. Imaging expression of the AR using a radiolabeled AR antagonist would enable non-invasive clinical staging and assessment of tumor heterogeneity via positron emission tomography (PET), complementing the findings of a [⁶⁸Ga]PSMA-11 scan. Previous efforts described the radiolabeling of enzalutamide with fluorine-18 but were limited by low molar activity. In this study, we showcase an efficient, reproducible automated synthesis of [¹⁸F]fluoroflutamide via zinc-mediated radiofluorination and assess its biodistribution in preclinical models of prostate cancer.Results\n\nFrom 1.87 Ci (69.19 GBq) of [¹⁸F]fluoride, [¹⁸F]fluoroflutamide was isolated with a non-decay-corrected radiochemical yield of 3.46 ± 1.30% (n = 4) and a radiochemical purity of > 99% in an average 79 min from end-of-beam using a bromoamide precursor. The average Am was 1.57 Ci/µmol (or 58.23 GBq/µmol) at the end of synthesis, and the radiochemical purity after 4 h was > 97%, indicating negligible radiolysis. A biodistribution and imaging study was performed using nude athymic mice with 22Rv1 human prostate cancer xenografts. From the results of this study, we observed a 'mass effect' in which carrier-added mice displayed an increased uptake of the tracer across most organs.Conclusions\n\nHerein, we report the optimized automated radiosynthesis of [¹⁸F]fluoroflutamide with high purity and sufficient yield for preclinical evaluation of AR-targeted imaging in mouse models of prostate cancer. The lack of uptake in androgen receptor-rich tissues and xenografts suggests impaired in vivo target engagement. While α-tertiary fluorination may attenuate CYP1A2-mediated oxidation to the higher-affinity 2-hydroxyflutamide metabolite, the observed signal is also consistent with reduced intrinsic AR affinity and/or altered pharmacokinetics of the fluorinated analog.",
  "abstract_shown": true,
  "affiliations": [
    "Division of Nuclear Medicine, Department of Radiology, University of Michigan Medical School, Ann Arbor, MI, 48109, USA.",
    "Division of Nuclear Medicine, Department of Radiology, University of Michigan Medical School, Ann Arbor, MI, 48109, USA. pjhscott@med.umich.edu.",
    "The Interdepartmental Program in Medicinal Chemistry, University of Michigan, Ann Arbor, MI, 48109, USA. pjhscott@med.umich.edu.",
    "Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA. jswright@upenn.edu."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Gina Kaup",
      "orcid": "0009-0003-1860-1226"
    },
    {
      "affs": [
        0
      ],
      "name": "Jason Anthony Witek",
      "orcid": "0000-0001-7271-6567"
    },
    {
      "affs": [
        0
      ],
      "name": "Shelbie Jaylene Cingoranelli",
      "orcid": "0009-0002-5578-0342"
    },
    {
      "affs": [
        0
      ],
      "name": "Jenelle Stauff"
    },
    {
      "affs": [
        0
      ],
      "name": "David Raffel",
      "orcid": "0000-0002-7188-9463"
    },
    {
      "affs": [
        0
      ],
      "name": "Allen Frederick Brooks",
      "orcid": "0000-0003-3773-3024"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Peter James Henry Scott",
      "orcid": "0000-0002-6505-0450"
    },
    {
      "affs": [
        3
      ],
      "name": "Jay Samuel Wright",
      "orcid": "0000-0002-1350-123X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/edbxpx3zne55s.bib",
  "cited_by": 0,
  "doi": "10.1186/s41181-026-00453-z",
  "fulltext_url": "https://europepmc.org/articles/PMC13677656",
  "id": "edbxpx3zne55s",
  "issns": [
    "2365-421X"
  ],
  "landing_url": "https://europepmc.org/article/MED/42894110",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "R895-920"
    ],
    [
      "lcc",
      "RM1-950"
    ],
    [
      "openalex",
      "2741|Radiopharmaceutical Chemistry and Applications"
    ]
  ],
  "openalex": "W7170085013",
  "pdf_url": "https://europepmc.org/articles/PMC13677656?pdf=render",
  "pmcid": "PMC13677656",
  "pmid": "42894110",
  "published": "2026-07-01",
  "publisher": "SpringerOpen",
  "ris": "https://research.draconitic.com/paper/edbxpx3zne55s.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:42Z",
      "native_id": "MED:42894110",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42894110"
    },
    {
      "first_seen": "2026-10-30T13:46:33Z",
      "native_id": "5f2c133be6644cdfb40628da5b0d86e0",
      "source": "doaj",
      "url": "https://doi.org/10.1186/s41181-026-00453-z"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2741|Radiopharmaceutical Chemistry and Applications",
      "subfield": "imaging"
    }
  ],
  "title": "Automated radiosynthesis and biodistribution of [¹⁸F]fluoroflutamide.",
  "title_text": "Automated radiosynthesis and biodistribution of [¹⁸F]fluoroflutamide.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:46:33Z",
  "url": "https://research.draconitic.com/paper/edbxpx3zne55s",
  "venue": "EJNMMI radiopharmacy and chemistry",
  "versions": []
}