Detection limit of 89Zr-labeled T cells for cellular tracking: an in vitro imaging approach using clinical PET/CT and PET/MRI

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 (t(1/2) = 78.4 h) has recently been used to synthesize [Zr-89]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 [Zr-89]Zr(oxinate)(4) utilizing clinical PET/CT and PET/MRI. Methods: Jurkat T cells were labeled with varying concentrations of [Zr-89]Zr(oxinate)(4) to generate different cell-specific activities (0.43-31.91 kBq/10(6) cells). Different concentrations of labeled cell suspensions (10(4), 10(5), and 10(6) cells) were seeded on 6-well plates and into a 3 x 3 cubic-well plate with 1 cm(3) cubic wells as a gel matrix. Plates were imaged on clinical PET/ CT and PET/MRI scanners for 30min. 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 x 10(4), when the specific activity was 27.8 kBq/10(6) cells. For the 3 x 3 cubic-well, a plate of 3.3 x 10(4) cells could be detected on images with a specific activity of 15.4 kBq/10(6) cells. Conclusion: The results show the feasibility of detecting [Zr-89]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.