Abstract
Simple SummaryTracking therapeutic cells with non-invasive imaging methods has the potential to provide important information on the efficacy of cell therapies. In oncology, for example, monitoring the spatial distribution of chimeric antigen receptor (CAR) T-cells or tumour-infiltrating lymphocytes (TILs) could be used to monitor the efficiency of cellular trafficking to target sites within a patient. This review covers different cell labelling approaches for the non-invasive detection of therapeutic cells using positron emission tomography (PET). The potential for the clinical translation of these approaches and first-in-human studies is examined, as well as the translational challenges involved and how imaging can help overcome some of these challenges.Cell therapy is a rapidly evolving field involving a wide spectrum of therapeutic cells for personalised medicine in cancer. In vivo imaging and tracking of cells can provide useful information for improving the accuracy, efficacy, and safety of cell therapies. This review focuses on radiopharmaceuticals for the non-invasive detection and tracking of therapeutic cells using positron emission tomography (PET). A range of approaches for imaging therapeutic cells is discussed: Direct ex vivo labelling of cells, in vivo indirect labelling of cells by utilising gene reporters, and detection of specific antigens expressed on the target cells using antibody-based radiopharmaceuticals (immuno-PET). This review examines the evaluation of PET imaging methods for therapeutic cell tracking in preclinical cancer models, their role in the translation into patients, first-in-human studies, as well as the translational challenges involved and how they can be overcome.
Highlights
Cell therapy is a rapidly evolving field and an important tool for personalised medicine in cancer
Direct labelling of cells has been used for tracking the fate, biodistribution, and migration behaviour of autologous patient-derived cells following administration into patients using [18 F]FDG ([18 F], t1/2 = 109.7 min), the most frequently used and widely available clinical positron emission tomography (PET) tracer in oncology, which is transported via glucose transporters (GLUT) and trapped intracellularly following phosphorylation by the enzyme hexokinase
These data could help predict and stratify which patients will respond to therapy as part of a personalised treatment and could be used to detect early response to therapy before changes in tumour size are apparent. In this way, labelling a small percentage of the injected therapeutic cell population could act as a companion biomarker for the larger proportion of cells used for the treatment
Summary
Cell therapy is a rapidly evolving field and an important tool for personalised medicine in cancer. A wide spectrum of therapeutic cells coined as “living drugs” has been developed in recent years for the treatment of cancer, with many undergoing clinical trials, and some licensed for clinical use These include tumour-infiltrating lymphocytes (TILs), chimeric antigen receptor (CAR) T-cells, natural killer (NK) cells, dendritic cells, macrophage-based therapies, and drug-loaded neutrophils. Recent development in total-body PET scanner technology to image the entire body has the potential to improve the sensitivity of detection by up to 40-fold for the whole body, and up to 5-fold for a single organ, and offers a promising tool to quantifiably track a very small number of labelled therapeutic cells in vivo [19]. The selection of the references was chosen to reflect a spectrum of applications and approaches, and was not based on defined search criteria
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