A proof-of-concept study to investigate the radiolabelling of human mesenchymal and hematopoietic stem cells with [89Zr]Zr-Df-Bz-NCS

Abstract

Abstract Background The transplantation of hematopoietic stem and progenitor cells (HSPCs) or mesenchymal stromal/stem cells (MSCs) for the treatment of a wide variety of diseases has been studied extensively. A challenge with cell-based therapies is that migration to and retention at the target site is often difficult to monitor and quantify. Zirconium-89 (89Zr) is a positron-emitting radionuclide with a half-life of 3.3 days, which allows long-term cell tracking. Para-isothiocyanatobenzyl-desferrioxamine B (Df-Bz-NCS) is the chelating agent of choice for 89Zr-cell surface labelling. We utilised a shortened labelling method, thereby avoiding a 30–60-min incubation step for [89Zr]Zr-Df-Bz-NCS chelation, to radiolabel HSPCs and MSCs with zirconium-89. Results Three 89Zr-MSC labelling attempts were performed. High labelling efficiencies (81.30 and 87.30%) and relatively good labelling yields (59.59 and 67.00%) were achieved with the use of a relatively larger number of MSCs (4.425 and 3.855 million, respectively). There was no significant decrease in MSC viability after 89Zr-labeling (p = 0.31). This labelling method was also translatable to prepare 89Zr-HSPC; preliminary data from one preparation indicated high 89Zr-HSPC labelling efficiency (88.20%) and labelling yield (71.06%), as well as good HSPC viability after labelling (68.65%). Conclusions Successful 89Zr-MSC and 89Zr-HSPC labelling was achieved, which underlines the prospects for in vivo cell tracking studies with positron emission tomography. In vitro investigations with larger sample sizes and preclinical studies are recommended.

Keywords

• Mesenchymal stem cells (MSCs)
• Hematopoietic stem and progenitor cells (HSPCs)
• Cell labelling
• In vivo cell tracking
• Zirconium-89
• Positron emission tomography