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.
Original language | English |
---|---|
Article number | 44233 |
Number of pages | 10 |
Journal | Scientific Reports |
Volume | 7 |
DOIs | |
Publication status | Published - 13 Mar 2017 |
Funding
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. We would like to thank the radiochemistry team within the Edinburgh Clinical Research Imaging Centre, as well as Dr. Susan Champion, Dr. Sally Pimlott and their team at the Greater Glasgow and Clyde NHS PET Centre for their crucial work and efforts to supply the radiotracers used in this study.
Keywords
- cell therapy
- cardiovascular disease
- positron emission tomography