"Imaging Triplets on Two Wheels": 61Cu-, 64Cu-, and 68Ga-labeled Bicyclic Peptides Targeting Nectin-4 Enable High-Contrast PET Imaging of Urothelial Carcinoma and Triple-Negative Breast Cancer.

@article{mauersberger2026imaging,
  title = {{"Imaging Triplets on Two Wheels": 61Cu-, 64Cu-, and 68Ga-labeled Bicyclic Peptides Targeting Nectin-4 Enable High-Contrast PET Imaging of Urothelial Carcinoma and Triple-Negative Breast Cancer.}},
  author = {Johanna Mauersberger and Tobias Krönke and Martin Ullrich and Markus Laube and Florian Brandt and Marc Pretze and Fabian Lohaus and Sebastian Hoberück and Christian Thomas and Matthias Miederer and Ralph A Bundschuh and Sven Stadlbauer and Klaus Kopka and Jens Pietzsch and Robert Wodtke},
  journal = {Bioconjugate chemistry},
  year = {2026},
  month = sep,
  doi = {10.1021/acs.bioconjchem.6c00366},
  url = {https://europepmc.org/article/MED/42915462},
  note = {CC BY},
}

TY  - JOUR
TI  - "Imaging Triplets on Two Wheels": 61Cu-, 64Cu-, and 68Ga-labeled Bicyclic Peptides Targeting Nectin-4 Enable High-Contrast PET Imaging of Urothelial Carcinoma and Triple-Negative Breast Cancer.
AU  - Johanna Mauersberger
AU  - Tobias Krönke
AU  - Martin Ullrich
AU  - Markus Laube
AU  - Florian Brandt
AU  - Marc Pretze
AU  - Fabian Lohaus
AU  - Sebastian Hoberück
AU  - Christian Thomas
AU  - Matthias Miederer
AU  - Ralph A Bundschuh
AU  - Sven Stadlbauer
AU  - Klaus Kopka
AU  - Jens Pietzsch
AU  - Robert Wodtke
PY  - 2026
DA  - 2026/09/01
JO  - Bioconjugate chemistry
DO  - 10.1021/acs.bioconjchem.6c00366
UR  - https://europepmc.org/article/MED/42915462
AB  - Nectin-4 is a validated target for theranostic approaches toward urothelial carcinoma, and radiolabeled ligands for PET and SPECT imaging are gaining increasing interest for noninvasive quantification of Nectin-4 prior to a targeted therapy. The goal of this study was to develop bicyclic peptides that allow radiolabeling with three different radionuclides (61Cu, 64Cu, and 68Ga) and to evaluate their suitability for high-contrast PET imaging in urothelial carcinoma (UC) and triple-negative breast cancer (TNBC). For this purpose, NECT-330, NECT-334, and NECT-346 were designed based on our previously developed ligand NECT-224 but harbor additional linker units between the bicyclic scaffold and the radiometal chelator. Binding kinetics to recombinant Nectin-4 and related isoforms were assessed by surface plasmon resonance (SPR) interaction analysis. Nectin-4-specific cell binding of the radiolabeled probes was determined using UC and TNBC cell lines, and PET/CT imaging was performed in respective tumor xenograft models. All novel ligands showed potent and selective binding to Nectin-4, with improved koff values compared to NECT-224. In small-animal PET/CT imaging studies, the most favorable properties were observed for [64Cu]Cu-NECT-334 (tumor-to-muscle of 20.8 and tumor-to-heart of 11.2) and [64Cu]Cu-NECT-346 (tumor-to-muscle of 15.5 and tumor-to-heart of 8.7) 1-2 h postinjection using a HT-1376 tumor model. Although the novel radioligands provided superior imaging properties to the previously developed radioligand [64Cu]Cu-NECT-224, a first-in-human application of the latter radioligand was initiated to assess the general suitability of PET/CT imaging in humans with a 64Cu-labeled bicyclic peptide directed to Nectin-4. Prospectively, the improved tumor-to-background contrasts achieved with the novel radioligands might further improve diagnostic accuracy and facilitate effective theranostic options in Nectin-4-expressing malignancies.
SN  - 1043-1802
SN  - 1520-4812
ER  -