MacAskill, M. G., Tavares, A. S., Wu, J., Lucatelli, C., Mountford, J. C., Baker, A. H., Newby, D. and Hadoke, P. W.F. (2017) PET cell tracking using (18)F-FLT is not limited by local reuptake of free radiotracer. Scientific Reports, 7, 44233. (doi: 10.1038/srep44233) (PMID:28287126) (PMCID:PMC5347009)
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Abstract
Assessing the retention of cell therapies following implantation is vital and often achieved by labelling cells with 2'-[(18)F]-fluoro-2'-deoxy-D-glucose ((18)F-FDG). However, this approach is limited by local retention of cell-effluxed radiotracer. Here, in a preclinical model of critical limb ischemia, we assessed a novel method of cell tracking using 3'-deoxy-3'-L-[(18)F]-fluorothymidine ((18)F-FLT); a clinically available radiotracer which we hypothesise will result in minimal local radiotracer reuptake and allow a more accurate estimation of cell retention. Human endothelial cells (HUVECs) were incubated with (18)F-FDG or (18)F-FLT and cell characteristics were evaluated. Dynamic positron emission tomography (PET) images were acquired post-injection of free (18)F-FDG/(18)F-FLT or (18)F-FDG/(18)F-FLT-labelled HUVECs, following the surgical induction of mouse hind-limb ischemia. In vitro, radiotracer incorporation and efflux was similar with no effect on cell viability, function or proliferation under optimised conditions (5 MBq/mL, 60 min). Injection of free radiotracer demonstrated a faster clearance of (18)F-FLT from the injection site vs. (18)F-FDG (p ≤ 0.001), indicating local cellular uptake. Using (18)F-FLT-labelling, estimation of HUVEC retention within the engraftment site 4 hr post-administration was 24.5 ± 3.2%. PET cell tracking using (18)F-FLT labelling is an improved approach vs. (18)F-FDG as it is not susceptible to local host cell reuptake, resulting in a more accurate estimation of cell retention.
Item Type: | Articles |
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Additional Information: | This work was funded by the Medical Research Council (MR/K00719X/1), The University of Edinburgh British Heart Foundation Core (RE/13/3/30183), The University of Edinburgh British Heart Foundation Centre for Vascular Regeneration (RM/13/2/30158) and The University of Edinburgh School of Clinical Sciences Funding Challenge. DEN is funded by the British Heart Foundation (CH/09/002) and is the recipient of a Wellcome Trust Senior Investigator Award (WT103782AIA). AHB is funded by the British Heart Foundation Chair of Translational Cardiovascular Sciences. |
Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Baker, Professor Andrew and Mountford, Dr Joanne |
Authors: | MacAskill, M. G., Tavares, A. S., Wu, J., Lucatelli, C., Mountford, J. C., Baker, A. H., Newby, D., and Hadoke, P. W.F. |
College/School: | College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health |
Journal Name: | Scientific Reports |
Publisher: | Nature Research |
ISSN: | 2045-2322 |
ISSN (Online): | 2045-2322 |
Published Online: | 13 March 2017 |
Copyright Holders: | Copyright © 2017 The Authors |
First Published: | First published in Scientific Reports 7:44233 |
Publisher Policy: | Reproduced under a creative commons license |
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