Pretargeted Immuno-PET Enables Monoclonal Antibody Imaging Beyond the Blood–Brain Barrier
Pretargeted PET imaging offers a powerful approach to improve nuclear imaging contrast and reduce systemic radiation exposure, yet its application in the brain has been limited by the blood-brain barrier (BBB). Here, we demonstrate, for the first time, successful pretargeted PET imaging of a brain target enabled by a bispecific antibody engineered for transferrin receptor-mediated BBB transcytosis. By combining this brain shuttle with a novel <sup>18</sup>F-labeled tetrazine, we achieve specific, quantifiable detection of brain-localized Aβ aggregates, validated through PET imaging and histological analysis. This proof-of-concept establishes a versatile, noninvasive imaging platform with broad potential for assessing biologic drug candidates and CNS targets previously considered intractable.
Authors
- Luca B. Gobbi (ORCID: https://orcid.org/0000-0002-0563-2491)
- Gitte M. Knudsen (ORCID: https://orcid.org/0000-0003-1508-6866)
- Blanca I. Aldana (ORCID: https://orcid.org/0000-0002-5027-1218)
- Lars Hvass (ORCID: https://orcid.org/0000-0003-2048-2409)
- Anne Skovsbo Clausen
- Matthias M. Herth (ORCID: https://orcid.org/0000-0002-7788-513X)
- Giuseppe Cannazza (ORCID: https://orcid.org/0000-0002-7347-7315)
- Andreas Kjær (ORCID: https://orcid.org/0000-0002-2706-5547)
- Thomas Kustermann (ORCID: https://orcid.org/0000-0003-3263-4174)
- Jens Niewoehner
- Umberto Maria Battisti (ORCID: https://orcid.org/0000-0002-1012-8644)
- Sara Lopes van den Broek (ORCID: https://orcid.org/0000-0002-3874-6962)
- Sophie Stotz (ORCID: https://orcid.org/0000-0003-4020-1088)
- Vladimir Shalgunov (ORCID: https://orcid.org/0000-0001-8956-1207)
- Tobias Gustavsson (ORCID: https://orcid.org/0009-0004-3672-2213)
- Michael Honer
- Elena Ferri (ORCID: https://orcid.org/0009-0000-0360-8538)
- Thomas Wuensche
Institutions
- Roche (Switzerland) (CH)
- University of Modena and Reggio Emilia (IT)
- University of Copenhagen (DK)
- Copenhagen University Hospital (DK)
- Rigshospitalet (DK)
Publication Details
- Journal
- Molecular Pharmaceutics
- Published
- 2025-11-06
- DOI
- https://doi.org/10.1021/acs.molpharmaceut.5c01180
- Citations
- 1
- Primary Topic
- Monoclonal and Polyclonal Antibodies Research
- Type
- article
- Field-Weighted Citation Impact
- 1.36
Funders
- Innovationsfonden
- European Commission
- Lundbeckfonden
- Novo Nordisk
- Rigshospitalet
- Faculty of Health and Medical Sciences, University of Western Australia
- Novo Nordisk Fonden
- H. Lundbeck A/S
- Det Sundhedsvidenskabelige Fakultet, Københavns Universitet
- Horizon 2020