Abstract
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.