A research team at the Technical University of Munich (TUM ) has developed a new method to visualize manipulated immune cells in the body. This should improve the understanding of cell therapies such as CAR T-cell therapy and make future treatments safer.

The principle: put simply, a second artificial receptor is inserted into the modified immune cells. The cells then become visible with the help of PET imaging and a specially developed, harmless radioactive “contrast agent”. If this so-called radioligand is injected into the body, it binds exclusively to the manipulated cells and their progeny, making them visible.

The process is based on artificial proteins with targeted binding properties, known as anticalins. These have been developed since the 1990s by Arne Skerra, Professor of Biological Chemistry at TUM and a pioneer in the field of protein design. This work resulted in an anticalin that binds the ligand DTPA and has now been harnessed as part of a cell surface receptor. A team led by Wolfgang Weber, Professor of Nuclear Medicine at the TUM Clinic, has used this as a basis to insert an artificial gene into cells that causes them to form the anticalin receptor “DTPA-R” on their surface. The project was led by Volker Morath and Katja Fritschle from the Department of Nuclear Medicine, who also developed the appropriate radioligand together with the team. Together with immunotherapy expert Dirk Busch, Professor of Medical Microbiology, Immunology and Hygiene at TUM, the procedure was tested with CAR-T cells.

In this way, the scientists were able to visualize in experiments with mice, for example, that the cells actually migrated to the affected diseased tissue and divided there. They were also able to show that the radioligand is rapidly excreted via the kidneys, binds exclusively to cells with the artificial receptor and does not interfere with other processes in the body. What’s more, the study showed that gene therapies in which viruses serve as a tool to change genetic information in cells can also be monitored in this way.

Original Paper:

Volker Morath, Katja Fritschle et al. “PET-based tracking of CAR T cells and viral gene transfer using a cell surface reporter that binds to lanthanide complexes”. Nature Biomedical Engineering (2025). DOI: 10.1038/s41551-025-01415-7

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