PET-based tracking of CAR T cells and viral gene transfer using a cell surface reporter that binds to lanthanide complexes
Abstrak
Abstract 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.
Penulis (18)
Volker Morath
Katja Fritschle
Linda Warmuth
Markus Anneser
Sarah Dötsch
Milica Živanić
Luisa Krumwiede
Philipp Bösl
Tarik Bozoglu
Stephanie Robu
Silvana Libertini
Susanne Kossatz
Christian Kupatt
Markus Schwaiger
Katja Steiger
Dirk H. Busch
Arne Skerra
Wolfgang A. Weber
Akses Cepat
- Tahun Terbit
- 2025
- Bahasa
- en
- Total Sitasi
- 7×
- Sumber Database
- CrossRef
- DOI
- 10.1038/s41551-025-01415-7
- Akses
- Open Access ✓