{
  "abstract": "Radioligand therapy targeting somatostatin receptors has emerged as a highly effective treatment strategy for neuroendocrine tumors, with growing evidence indicating that SST₂ antagonists and dual SST₂/SST₅ targeting approaches may further enhance tumor coverage and therapeutic efficacy. In this study, DOTA-NOC, a somatostatin analog with high affinity for SST₂ and SST₅, served as the scaffold for the design of novel ligands incorporating structural features associated with receptor antagonism. The resulting ligands were conjugated to DOTA for ¹⁷⁷Lu radiolabeling and evaluated for receptor affinity, antagonistic potency, and in vivo properties. Among the series, ¹⁷⁷Lu-10 displayed high affinity for both receptor subtypes while acting selectively as an SST₅ antagonist. Compared to [¹⁷⁷Lu]Lu-DOTA-NOC, it showed similar SST₂ tumor uptake but nearly 5-fold higher accumulation in SST₅-expressing tumors. This work provides new insights into the structural determinants underlying SST₂ and SST₅ affinity, selectivity, and antagonistic behavior, demonstrating that receptor recognition and functional activity arise from the combined contribution of multiple structural elements and supporting the development of dual SST₂/SST₅-targeted radioligands.",
  "abstract_shown": true,
  "affiliations": [
    "Division of Radiopharmaceutical Chemistry, Department Theragnostics, University Hospital Basel, University of Basel Basel 4031 Switzerland rosalba.mansi@usb.ch melpomeni.fani@usb.ch +41(0)61 556 58 91.",
    "Institute of Pharmacology and Toxicology, University Hospital Jena, Friedrich Schiller University Jena 07747 Germany."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Fabienne Spinnler"
    },
    {
      "affs": [
        0
      ],
      "name": "Luigi Del Pozzo"
    },
    {
      "affs": [
        0
      ],
      "name": "Lennart Bohrmann"
    },
    {
      "affs": [
        0
      ],
      "name": "Sandra Zanger"
    },
    {
      "affs": [
        1
      ],
      "name": "Nina Kathleen Blum",
      "orcid": "0000-0002-9598-0325"
    },
    {
      "affs": [
        1
      ],
      "name": "Monique Brendel"
    },
    {
      "affs": [
        1
      ],
      "name": "Stefan Schulz"
    },
    {
      "affs": [
        0
      ],
      "name": "Rosalba Mansi",
      "orcid": "0000-0003-0342-8865"
    },
    {
      "affs": [
        0
      ],
      "name": "Melpomeni Fani",
      "orcid": "0000-0002-9309-1604"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bvdz5ztzv2vz2.bib",
  "cited_by": 0,
  "doi": "10.1039/d6md00646a",
  "fulltext_url": "https://europepmc.org/articles/PMC13637744",
  "id": "bvdz5ztzv2vz2",
  "issns": [
    "2632-8682"
  ],
  "landing_url": "https://europepmc.org/article/MED/42836142",
  "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": [
    [
      "openalex",
      "2741|Radiopharmaceutical Chemistry and Applications"
    ]
  ],
  "openalex": "W7220455835",
  "pdf_url": "https://europepmc.org/articles/PMC13637744?pdf=render",
  "pmcid": "PMC13637744",
  "pmid": "42836142",
  "published": "2026-10-05",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/bvdz5ztzv2vz2.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:10Z",
      "native_id": "MED:42836142",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42836142"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2741|Radiopharmaceutical Chemistry and Applications",
      "subfield": "imaging"
    }
  ],
  "title": "Development of dual SST₂/SST₅ targeting radioligands through rational structural design.",
  "title_text": "Development of dual SST₂/SST₅ targeting radioligands through rational structural design.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:10Z",
  "url": "https://research.draconitic.com/paper/bvdz5ztzv2vz2",
  "venue": "RSC medicinal chemistry",
  "versions": []
}