A novel PET imaging system has been developed to track CAR T cells and viral gene transfer, utilizing a cell surface reporter that binds to lanthanide complexes, which addresses the challenges in monitoring advanced therapy medicinal products (ATMPs).

This innovative reporter gene system is based on anticalins—engineered proteins that specifically bind to ligands—allowing for the in vivo detection of CAR T cells and gene therapies.

Existing tracking methods, such as direct ex vivo labeling with iron oxide particles, are limited in assessing cell proliferation due to label dilution and persistence after cell death.

Dynamic PET imaging in mouse models has demonstrated rapid renal clearance of the radioligand and high specificity for tumors expressing the DTPA-R reporter, indicating the potential for effective imaging of CAR T cells.

While an indirect labeling strategy using endogenous biomarkers or synthetic reporter genes could improve tracking, traditional optical imaging techniques are limited by tissue scattering and absorption.

The successful integration of the DTPA-R reporter into CAR T cells enables real-time monitoring of their expansion and infiltration at tumor sites through PET imaging.

Longitudinal studies have confirmed the system's ability to quantitatively assess CAR T cell numbers and their therapeutic efficacy against tumors, underscoring the significance of imaging in optimizing CAR T cell therapies.

Despite the promise of current gene therapies and CAR T cell treatments in clinical settings, their development is often hindered by limited methods for tracking biodistribution and persistence in vivo.

Positron emission tomography (PET) is proposed as a viable solution, offering depth-independent, quantitative imaging capabilities that are suitable for both preclinical and clinical applications.

To enhance the system's functionality, two variants of the reporter protein were created, each with unique binding specificities, and tested across various human cell lines.

An ideal reporter system is characterized by being small, non-immunogenic, and allowing for straightforward radiolabeling with commonly used radioisotopes like fluorine-18.