Evaluation of different ⁸⁹Zr-labeled synthons for direct labeling and tracking of white blood cells and stem cells in healthy athymic mice

Cell based therapies are evolving as an effective new approach to treat various diseases. To understand the safety, efficacy, and mechanism of action of cell-based therapies, it is imperative to follow their biodistribution noninvasively. Positron-emission-tomography (PET)-based non-invasive imaging of cell trafficking offers such a potential. Herein, we evaluated and compared three different ready-to-use direct cell radiolabeling synthons, [⁸⁹Zr]Zr-DFO-Bn-NCS, [⁸⁹Zr]Zr-Hy₃ADA⁵-NCS, and [⁸⁹Zr]Zr-Hy₃ADA⁵-SA for PET imaging-based trafficking of white blood cells (WBCs) and stem cells (SCs) up to 7 days in athymic nude mice. We compared the degree of ⁸⁹Zr complexation and percentage of cell radiolabeling efficiencies with each. All three synthons, [⁸⁹Zr]Zr-DFO-Bn-NCS, [⁸⁹Zr]Zr-Hy₃ADA⁵-NCS, and [⁸⁹Zr]Zr-Hy₃ADA⁵-SA, were successfully prepared, and used for radiolabeling of WBCs and SCs. The highest cell radiolabeling yield was found for [⁸⁹Zr]Zr-DFO-Bn-NCS, followed by [⁸⁹Zr]Zr-Hy₃ADA⁵-NCS, and [⁸⁹Zr]Zr-Hy₃ADA⁵-SA. In terms of biodistribution, WBCs radiolabeled with [⁸⁹Zr]Zr-DFO-Bn-NCS or [⁸⁹Zr]Zr-Hy₃ADA⁵-NCS, were primarily accumulated in liver and spleen, whereas SCs radiolabeled with [⁸⁹Zr]Zr-DFO-Bn-NCS or [⁸⁹Zr]Zr-Hy₃ADA⁵-NCS were found in lung, liver and spleen. A high bone uptake was observed for both WBCs and SCs radiolabeled with [⁸⁹Zr]Zr-Hy₃ADA⁵-SA, suggesting in-vivo instability of [⁸⁹Zr]Zr-Hy₃ADA⁵-SA synthon. This study offers an appropriate selection of ready-to-use radiolabeling synthons for noninvasive trafficking of WBCs, SCs and other cell-based therapies.