Radiolabelling of Polyclonally Expanded Human Regulatory T Cells (Treg) with 89Zr-oxine for Medium-Term In Vivo Cell Tracking
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Published:2023-02-03
Issue:3
Volume:28
Page:1482
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ISSN:1420-3049
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Container-title:Molecules
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language:en
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Short-container-title:Molecules
Author:
Jacob Jacinta1, Volpe Alessia2, Peng Qi12ORCID, Lechler Robert I.1, Smyth Lesley A.3, Lombardi Giovanna1, Fruhwirth Gilbert O.2ORCID
Affiliation:
1. MRC Centre for Transplantation, Peter Gorer Department of Immunobiology, School of Immunology and Microbial Science, King’s College London, Guy’s Hospital, Tower Wing, 5th Floor, Great Maze Pond, London SE1 9RT, UK 2. Imaging Therapies and Cancer Group, Comprehensive Cancer Centre, School of Cancer and Pharmaceutical Sciences, King’s College London, Guy’s Campus, New Hunt’s House, 2nd Floor, Great Maze Pond, London SE1 1UL, UK 3. School of Health, Sport and Bioscience, Stratford Campus, University of East London, London E15 4LZ, UK
Abstract
Regulatory T cells (Tregs) are a promising candidate cell therapy to treat autoimmune diseases and aid the longevity of transplanted solid organs. Despite increasing numbers of clinical trials using human Treg therapy, important questions pertaining to their in vivo fate, distribution, and function remain unanswered. Treg accumulation in relevant tissues was found to be crucial for Treg therapy efficacy, but existing blood-borne biomarkers are unlikely to accurately reflect the tissue state. Non-invasive Treg tracking by whole-body imaging is a promising alternative and can be achieved by direct radiolabelling of Tregs and following the radiolabelled cells with positron emission tomography (PET). Our goal was to evaluate the radiolabelling of polyclonal Tregs with 89Zr to permit their in vivo tracking by PET/CT for longer than one week with current preclinical PET instrumentation. We used [89Zr]Zr(oxinate)4 as the cell-labelling agent and achieved successful radiolabelling efficiency of human Tregs spanning 0.1–11.1 Bq 89Zr/Treg cell, which would be compatible with PET tracking beyond one week. We characterized the 89Zr-Tregs, assessing their phenotypes, and found that they were not tolerating these intracellular 89Zr amounts, as they failed to survive or expand in a 89Zr-dose-dependent manner. Even at 0.1 Bq 89Zr per Treg cell, while 89Zr-Tregs remained functional as determined by a five-day-long effector T cell suppression assay, they failed to expand beyond day 3 in vitro. Moreover, PET imaging revealed signs of 89Zr-Treg death after adoptive transfer in vivo. In summary, 89Zr labelling of Tregs at intracellular radioisotope amounts compatible with cell tracking over several weeks did not achieve the desired outcomes, as 89Zr-Tregs failed to expand and survive. Consequently, we conclude that indirect Treg labelling is likely to be the most effective alternative method to satisfy the requirements of this cell tracking scenario.
Funder
British Heart Foundation MRC Centre for Transplantation at KCL Cancer Research UK Wellcome/EPSRC Centre for Medical Engineering National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London and/or the NIHR Clinical Research Facility
Subject
Chemistry (miscellaneous),Analytical Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Molecular Medicine,Drug Discovery,Pharmaceutical Science
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