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Purpose Tracking cells in vivo using imaging can provide non-invasive information to understand the pharmacology, efficacy, and safety of novel cell therapies. Zirconium-89 (t1/2 = 78.4 h) has recently been used to synthesize [89Zr]Zr(oxinate)4 for cell tracking using positron emission tomography (PET). This work presents an in vitro approach to estimate the detection limit for in vivo PET imaging of Jurkat T cells directly labeled with [89Zr]Zr(oxinate)4 utilizing clinical PET/CT and PET/MRI. Methods Jurkat T cells were labeled with varying concentrations of [89Zr]Zr(oxinate)4 to generate different cell-specific activities (0.43–31.91 kBq/106 cells). Different concentrations of labeled cell suspensions (104, 105, and 106 cells) were seeded on 6-well plates and into a 3 × 3 cubic-well plate with 1 cm3 cubic wells as a gel matrix. Plates were imaged on clinical PET/CT and PET/MRI scanners for 30 min. The total activity in each well was determined by drawing volumes of interest over each well on PET images. The total cell-associated activity was measured using a well counter and correlated with imaging data. Simulations for non-specific signal were performed to model the effect of non-specific radioactivity on detection. Results Using this in vitro model, the lowest cell number that could be visualized on 6-well plate images was 6.8 × 104, when the specific activity was 27.8 kBq/106 cells. For the 3 × 3 cubic-well, a plate of 3.3 × 104 cells could be detected on images with a specific activity of 15.4 kBq/106 cells. Conclusion The results show the feasibility of detecting [89Zr]Zr(oxinate)4-labeled Jurkat T cells on clinical PET systems. The results provide a best-case scenario, as in vivo detection using PET/CT or PET/MRI will be affected by cell number, specific activity per cell, the density of cells within the target volume, and non-specific signal. This work has important implications for cell labeling studies in patients, particularly when using radiosensitive cells (e.g., T cells), which require detection of low cell numbers while minimizing radiation dose per cell.

Simple Summary Tracking 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. Abstract 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.

Neutrophils are the first line of defense against pathogens and abnormal cells. They regulate many biological processes such as infections and inflammation. Increasing evidence demonstrated a role for neutrophils in cancer, where different subpopulations have been found to possess both pro- or anti-tumorigenic functions in the tumor microenvironment. In this review, we discuss the phenotypic and functional diversity of neutrophils in cancer, their prognostic significance, and therapeutic relevance in human and preclinical models. Molecular imaging methods are increasingly used to probe neutrophil biology in vivo, as well as the cellular changes that occur during tumor progression and over the course of treatment. This review will discuss the role of neutrophil imaging in oncology and the lessons that can be drawn from imaging in infectious diseases and inflammatory disorders. The major factors to be considered when developing imaging techniques and biomarkers for neutrophils in cancer are reviewed. Finally, the potential clinical applications and the limitations of each method are discussed, as well as the challenges for future clinical translation.

Targeting specific cell membrane markers for both diagnostic imaging and radionuclide therapy is a rapidly evolving field in cancer research. Some of these applications have now found a role in routine clinical practice and have been shown to have a significant impact on patient management. Several molecular targets are being investigated in ongoing clinical trials and show promise for future implementation. Advancements in molecular biology have facilitated the identification of new cancer-specific targets for radiopharmaceutical development.

Purpose Tracking cells in vivo using imaging can provide non-invasive information to understand the pharmacology, efficacy, and safety of novel cell therapies. Zirconium-89 (t1/2 = 78.4 h) has recently been used to synthesize [89Zr]Zr(oxinate)4 for cell tracking using positron emission tomography (PET). This work presents an in vitro approach to estimate the detection limit for in vivo PET imaging of Jurkat T cells directly labeled with [89Zr]Zr(oxinate)4 utilizing clinical PET/CT and PET/MRI. Methods Jurkat T cells were labeled with varying concentrations of [89Zr]Zr(oxinate)4 to generate different cell-specific activities (0.43–31.91 kBq/106 cells). Different concentrations of labeled cell suspensions (104, 105, and 106 cells) were seeded on 6-well plates and into a 3 × 3 cubic-well plate with 1 cm3 cubic wells as a gel matrix. Plates were imaged on clinical PET/CT and PET/MRI scanners for 30 min. The total activity in each well was determined by drawing volumes of interest over each well on PET images. The total cell-associated activity was measured using a well counter and correlated with imaging data. Simulations for non-specific signal were performed to model the effect of non-specific radioactivity on detection. Results Using this in vitro model, the lowest cell number that could be visualized on 6-well plate images was 6.8 × 104, when the specific activity was 27.8 kBq/106 cells. For the 3 × 3 cubic-well, a plate of 3.3 × 104 cells could be detected on images with a specific activity of 15.4 kBq/106 cells. Conclusion The results show the feasibility of detecting [89Zr]Zr(oxinate)4-labeled Jurkat T cells on clinical PET systems. The results provide a best-case scenario, as in vivo detection using PET/CT or PET/MRI will be affected by cell number, specific activity per cell, the density of cells within the target volume, and non-specific signal. This work has important implications for cell labeling studies in patients, particularly when using radiosensitive cells (e.g., T cells), which require detection of low cell numbers while minimizing radiation dose per cell.

Glucose metabolism in tumours is reprogrammed away from oxidative metabolism, even in the presence of oxygen. Non-invasive imaging techniques can probe these alterations in cancer metabolism providing tools to detect tumours and their response to therapy. Although Positron Emission Tomography with ((18)F)2-fluoro-2-deoxy-D-glucose ((18)F-FDG PET) is an established clinical tool to probe cancer metabolism, it has poor spatial resolution and soft tissue contrast, utilizes ionizing radiation and only probes glucose uptake and phosphorylation and not further downstream metabolism. Magnetic Resonance Spectroscopy (MRS) has the capability to non-invasively detect and distinguish molecules within tissue but has low sensitivity and can only detect selected nuclei. Dynamic Nuclear Polarization (DNP) is a technique which greatly increases the signal-to-noise ratio (SNR) achieved with MR by significantly increasing nuclear spin polarization and this method has now been translated into human imaging. This review provides a brief overview of this process, also termed Hyperpolarized Carbon-13 Magnetic Resonance Spectroscopic Imaging (HP (13)C-MRSI), its applications in preclinical imaging, an outline of the current human trials that are ongoing, as well as future potential applications in oncology.