Dataset Information

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

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.

SUBMITTER: Lechermann LM

PROVIDER: S-EPMC7360010 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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

Lechermann Laura M LM Manavaki Roido R Attili Bala B Lau Doreen D Jarvis Lorna B LB Fryer Tim D TD Bird Nick N Aloj Luigi L Patel Neel N Basu Bristi B Cleveland Matthew M Aigbirhio Franklin I FI Jones Joanne L JL Gallagher Ferdia A FA

EJNMMI research 20200714 1

<h4>Purpose</h4>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]Z ...[more]

PMID: 32666311

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