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

Macaskill, Mark G. and Tavares, Adriana S. and Wu, Junxi and Lucatelli, Christophe and Mountford, Joanne C. and Baker, Andrew H. and Newby, David E. and Hadoke, Patrick W.F. (2017) PET cell tracking using 18 F-FLT is not limited by local reuptake of free radiotracer. Scientific Reports, 7. 44233. ISSN 2045-2322

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    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.