DOTA-based plectin-1 targeted contrast agent enables detection of pancreatic cancer in human tissue.

DOTA PDAC fluorescent imaging plectin-1 tissue imaging

Journal

Angewandte Chemie (International ed. in English)
ISSN: 1521-3773
Titre abrégé: Angew Chem Int Ed Engl
Pays: Germany
ID NLM: 0370543

Informations de publication

Date de publication:
12 Apr 2024
Historique:
revised: 12 03 2024
received: 02 12 2023
accepted: 29 03 2024
medline: 12 4 2024
pubmed: 12 4 2024
entrez: 12 4 2024
Statut: aheadofprint

Résumé

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive and lethal malignancy with extremely poor patient survival rates. A key reason for the poor prognosis is the lack of effective diagnostic tools to detect the disease at curable, premetastatic stages. Tumor surgical resection is PDAC first-line treatment, however distinguishing between cancerous and healthy tissue with current imaging tools remains a challenge. In this work, we report a DOTA-based fluorescent probe targeting plectin-1 for imaging PDAC with high specificity. To enable heterogeneous functionalization of the DOTA-core with multiple targeting peptide units and the fluorophore, a novel, fully clickable synthetic route that proceeds in one-pot was developed. Extensive validation of the probe set the stage for PDAC detection in mice and human tissue. Altogether, these findings may pave the way for improved clinical understanding and early detection of PDAC progression as well as more accurate resection criteria.

Identifiants

pubmed: 38608197
doi: 10.1002/anie.202318485
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e202318485

Informations de copyright

© 2024 Wiley‐VCH GmbH.

Auteurs

Thais Gazzi (T)

Leibniz Research Institute for Molecular Pharmacology, Medicinal Chemistry, GERMANY.

Marina Lesina (M)

Technical University of Munich, CCCM, GERMANY.

Qinghua Wang (Q)

Chinese Academy of Medical Sciences & Peking Union Medical College Institute of Materia Medica, State Key Laboratory of Bioactive Substances and Function of Natural Medicine es and Function of Natural Medicine, CHINA.

Alexandra Berninger (A)

Technical University of Munich, CCCM, GERMANY.

Silke Radetzki (S)

Leibniz Research Institute for Molecular Pharmacology, Screening Unit, GERMANY.

Ihsan Ekin Demir (IE)

Technical University of Munich, CCCM, GERMANY.

Larissa Heinemann (L)

Technical University of Munich, CCCMg, GERMANY.

Waldemar Meiser (W)

Leibniz Research Institute for Molecular Pharmacology, Medicinal Chemistry, GERMANY.

Sebastian Wilke (S)

Leibniz Research Institute for Molecular Pharmacology, Medicinal Chemistry, GERMANY.

Jens Peter von Kries (J)

Leibniz Research Institute for Molecular Pharmacology, Screening Unit, GERMANY.

Hana Algül (H)

Technical University of Munich, CCCM, GERMANY.

Hai-Yu Hu (HY)

Chinese Academy of Medical Sciences & Peking Union Medical College Institute of Materia Medica, State Key Laboratory of Bioactive Substances and Function of Natural Medicine es and Function of Natural Medicine, CHINA.

Marc Nazaré (M)

Leibniz-Forschungsinstitut für Molekulare Pharmakologie im Forschungsverbund Berlin e.V. (FMP), Chemische Biologie, Robert-Roessle-Str. 10, Campus Berlin-Buch, 13125, Berlin, GERMANY.

Classifications MeSH