PET cell tracking using (18)F-FLT is not limited by local reuptake of free radiotracer

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
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 > Institute of Cardiovascular and Medical Sciences
Journal Name:Scientific Reports
Publisher:Nature Publishing Group
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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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
587191TRANSLATING HUMAN EMBRYONIC STEM CELL-DERIVED ENDOTHELIAL CELL THERAPY TO THE CLINICAndrew BakerMedical Research Council (MRC)MR/K00719X/1RI CARDIOVASCULAR & MEDICAL SCIENCES
637071BHF Centre for regenerative medicineAndrew BakerBritish Heart Foundation (BHF)RM/13/2/30158RI CARDIOVASCULAR & MEDICAL SCIENCES