title: PET Cell Tracking Using18F-FLT is Not Limited by Local Reuptake of Free Radiotracer.
abstract: Assessing the retention of cell therapies following implantation is vital and often achieved by labelling cells with 2'-[18F]-fluoro-2'-deoxy-D-glucose (18F-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-[18F]-fluorothymidine (18F-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 with18F-FDG or18F-FLT and cell characteristics were evaluated. Dynamic positron emission tomography (PET) images were acquired post-injection of free18F-FDG/18F-FLT or18F-FDG/18F-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 of18F-FLT from the injection site vs.18F-FDG (p ≤ 0.001), indicating local cellular uptake. Using18F-FLT-labelling, estimation of HUVEC retention within the engraftment site 4 hr post-administration was 24.5 ± 3.2%. PET cell tracking using18F-FLT labelling is an improved approach vs.18F-FDG as it is not susceptible to local host cell reuptake, resulting in a more accurate estimation of cell retention.
authors.affiliation: University/BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
authors.forename: Mark G
authors.initials: MG
authors.lastname: MacAskill
authors.affiliation: University/BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
authors.forename: Adriana S
authors.initials: AS
authors.lastname: Tavares
authors.affiliation: University/BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
authors.forename: Junxi
authors.initials: J
authors.lastname: Wu
authors.affiliation: Clinical Research Imaging Centre, University of Edinburgh, Edinburgh, UK.
authors.forename: Christophe
authors.initials: C
authors.lastname: Lucatelli
authors.affiliation: Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Joanne C
authors.initials: JC
authors.lastname: Mountford
authors.affiliation: University/BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Baker
authors.affiliation: University/BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
authors.forename: David E
authors.initials: DE
authors.lastname: Newby
authors.affiliation: University/BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
authors.forename: Patrick W F
authors.initials: PW
authors.lastname: Hadoke
mesh_terms: D058948:Cell Tracking / Q000379:methods*; D015224:Dideoxynucleosides / Q000493:pharmacokinetics / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D000072078:Positron Emission Tomography Computed Tomography; D011849:Radioactive Tracers
chemical_list: D015224:Dideoxynucleosides; D011849:Radioactive Tracers; C002854:alovudine