Year: 2025
Type: article
Abstract: High Resolution Image Download MS PowerPoint Slide 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 18 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.
Source: Molecular Pharmaceutics
Authors: Tobias Gustavsson, Thomas Kustermann, Lars Hvass, Thomas E. Wuensche, Anne Skovsbo Clausen, Sophie Stotz, Vladimir Shalgunov, Sara Lopes van den Broek, Gitte M. Knudsen, Blanca Aldana, Elena Ferri, Giuseppe Cannazza, Jens Niewoehner, Luca Gobbi, Michael Honer, Umberto Maria Battisti, Andreas Kjaer, Matthias M. Herth
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,500
Funders: Kræftens Bekæmpelse, Innovationsfonden, European Commission, Lundbeckfonden, Novo Nordisk, Danmarks Frie Forskningsfond, Rigshospitalet, Faculty of Health and Medical Sciences, University of Western Australia, Novo Nordisk Fonden, H. Lundbeck A/S, Horizon 2020 Framework Programme, Det Sundhedsvidenskabelige Fakultet, Københavns Universitet, Horizon 2020, HORIZON EUROPE Marie Sklodowska-Curie Actions
Awards: G1073912976, G186104510, G258300446, Nerve Growth Factor Delivery into the Brain – focus on therapeutic potential in Alzheimer’s disease and In Vivo Evaluation via PET, G434337789, G487296194, G5466177950, G581189433, G5857062797, G6753707462, “In Vivo Click PET Imaging Agents”: Improving clinical companion diagnostics
OpenAlex ID: W4415977706