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

EJNMMI Research

Joanne L. Jones¹  Lorna B. Jarvis¹  Nick Bird²  Bristi Basu³  Luigi Aloj⁴  Doreen Lau⁴  Roido Manavaki⁴  Bala Attili⁴  Ferdia A. Gallagher⁴  Laura M. Lechermann⁴  Matthew Cleveland⁵  Tim D. Fryer⁶  Neel Patel⁶  Franklin I. Aigbirhio⁶ 

[1] Department of Clinical Neurosciences, University of Cambridge;Department of Nuclear Medicine, Addenbrooke’s Hospital;Department of Oncology, University of Cambridge;Department of Radiology, University of Cambridge;GSK Medicines Research Centre;Wolfson Brain Imaging Centre, University of Cambridge;

关键词: PET;    Cell labeling;    Cell tracking;    Zirconium-89;    Detection limit;   

DOI  :  10.1186/s13550-020-00667-5

来源: DOAJ

【 摘 要 】

Abstract 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 [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.

【 授权许可】

Unknown