PET-based tracking of CAR T cells and viral gene transfer using a cell surface reporter that binds to lanthanide complexes
The clinical translation of cell- and gene-based therapies is limited by the lack of non-invasive, quantitative and specific whole-body imaging tools. Here we present a positron emission tomography reporter system based on a membrane-anchored anticalin protein that binds a fluorine-18-labelled lanthanide complex with picomolar affinity via a bio-orthogonal interaction. The reporter was introduced into therapeutic cells, including CAR T cells and adeno-associated virus-transduced cells. In vitro, reporter expression conferred >800-fold higher radioligand binding versus controls. In mice, the radioligand demonstrated rapid renal clearance, showed no off-target accumulation and enabled high-contrast detection of as few as 1,200 CAR T cells in the bone marrow. Longitudinal positron emission tomography imaging over 4 weeks revealed precise tracking of CAR T cell expansion and migration, with signal intensity correlating linearly with flow cytometry data. The system also enabled the quantitative imaging of in vivo gene transfer using an adeno-associated viral vector. This depth-independent whole-body imaging platform offers a powerful tool for monitoring therapeutic cell dynamics and gene delivery in preclinical and potentially clinical settings.
Authors
- Markus Schwaiger (ORCID: https://orcid.org/0000-0002-2305-7144)
- Katja Steiger (ORCID: https://orcid.org/0000-0002-7269-5433)
- Katja Fritschle (ORCID: https://orcid.org/0000-0002-5443-9663)
- Linda Warmuth (ORCID: https://orcid.org/0000-0003-3324-7731)
- Silvana Libertini (ORCID: https://orcid.org/0000-0003-2633-1564)
- Stephanie Robu
- Tarik M. Bozoglu (ORCID: https://orcid.org/0000-0002-6545-2150)
- Sarah Dötsch (ORCID: https://orcid.org/0000-0003-1712-4619)
- Arne Skerra (ORCID: https://orcid.org/0000-0002-5717-498X)
- Susanne Kossatz (ORCID: https://orcid.org/0000-0002-1908-1782)
- Volker Morath (ORCID: https://orcid.org/0000-0001-7636-0537)
- Milica Živanić (ORCID: https://orcid.org/0000-0002-4967-5709)
- Christian Kupatt (ORCID: https://orcid.org/0000-0002-3611-1218)
- Dirk Hans Busch (ORCID: https://orcid.org/0000-0001-8713-093X)
- Markus R. Anneser (ORCID: https://orcid.org/0000-0002-8876-4747)
- Luisa Krumwiede (ORCID: https://orcid.org/0000-0001-5695-1575)
- Wolfgang Weber (ORCID: https://orcid.org/0000-0002-7854-4345)
- P Bösl
Institutions
- Novartis (Switzerland) (CH)
- TUM Klinikum (DE)
- Deutsches Herzzentrum der Charité (DE)
- German Cardiac Society (DE)
- Institute of Medical Microbiology and Hygiene (DE)
- Weber and Weber (Germany) (DE)
- Technical University of Munich (DE)
Publication Details
- Journal
- Nature Biomedical Engineering
- Published
- 2025-06-13
- DOI
- https://doi.org/10.1038/s41551-025-01415-7
- Citations
- 8
- Primary Topic
- CAR-T cell therapy research
- Type
- article
- Field-Weighted Citation Impact
- 8.36
Funders
- National Centre for the Replacement Refinement and Reduction of Animals in Research