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Published in: EJNMMI Research 1/2020

01-12-2020 | Magnetic Resonance Imaging | Original research

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

Authors: Laura M. Lechermann, Roido Manavaki, Bala Attili, Doreen Lau, Lorna B. Jarvis, Tim D. Fryer, Nick Bird, Luigi Aloj, Neel Patel, Bristi Basu, Matthew Cleveland, Franklin I. Aigbirhio, Joanne L. Jones, Ferdia A. Gallagher

Published in: EJNMMI Research | Issue 1/2020

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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 (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.
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Metadata
Title
Detection limit of 89Zr-labeled T cells for cellular tracking: an in vitro imaging approach using clinical PET/CT and PET/MRI
Authors
Laura M. Lechermann
Roido Manavaki
Bala Attili
Doreen Lau
Lorna B. Jarvis
Tim D. Fryer
Nick Bird
Luigi Aloj
Neel Patel
Bristi Basu
Matthew Cleveland
Franklin I. Aigbirhio
Joanne L. Jones
Ferdia A. Gallagher
Publication date
01-12-2020
Publisher
Springer Berlin Heidelberg
Published in
EJNMMI Research / Issue 1/2020
Electronic ISSN: 2191-219X
DOI
https://doi.org/10.1186/s13550-020-00667-5

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