In Vivo PET Imaging of Monocytes Labeled with [89Zr]Zr-PLGA-NH2 Nanoparticles in Tumor and Staphylococcus aureus Infection Models

Simple Summary: Immune cells are increasingly used for therapy in cancer and other diseases. To better understand immune-cell kinetics, cell-tracking with highly sensitive imaging modalities is required. The aim of this study was to develop a new strategy for the in vivo tracking of a small number of cells, using positron emission tomography (PET). We labeled poly(lactic-co-glycolic acid) nanoparticles containing a primary endcap (PLGA-NH2) with the radionuclide zirconium-89. The nanoparticles were characterized for size, polydispersity index, zetapotential and radiolabel retention. Subsequently, they were used for the ex vivo radiolabeling of a monocyte cell line (THP-1). We demonstrated that these radiolabeled monocyte cells can be traced in vivo in mouse tumor and infection models. The exponential growth of research on cell-based therapy is in major need of reliable and sensitive tracking of a small number of therapeutic cells to improve our understanding of the in vivo cell-targeting properties. In-111-labeled poly(lactic-co-glycolic acid) with a primary amine endcap nanoparticles ([In-111]In-PLGA-NH2 NPs) were previously used for cell labeling and in vivo tracking, using SPECT/CT imaging. However, to detect a low number of cells, a higher sensitivity of PET is preferred. Therefore, we developed Zr-89-labeled NPs for ex vivo cell labeling and in vivo cell tracking, using PET/MRI. We intrinsically and efficiently labeled PLGA-NH2 NPs with [Zr-89]ZrCl4. In vitro, [Zr-89]Zr-PLGA-NH2 NPs retained the radionuclide over a period of 2 weeks in PBS and human serum. THP-1 (human monocyte cell line) cells could be labeled with the NPs and retained the radionuclide over a period of 2 days, with no negative effect on cell viability (specific activity 279 +/- 10 kBq/10(6) cells). PET/MRI imaging could detect low numbers of [Zr-89]Zr-THP-1 cells (10,000 and 100,000 cells) injected subcutaneously in Matrigel. Last, in vivo tracking of the [Zr-89]Zr-THP-1 cells upon intravenous injection showed specific accumulation in local intramuscular Staphylococcus aureus infection and infiltration into MDA-MB-231 tumors. In conclusion, we showed that [Zr-89]Zr-PLGA-NH2 NPs can be used for immune-cell labeling and subsequent in vivo tracking of a small number of cells in different disease models.

Automated summary

This study successfully demonstrated in vivo tracking of a small number of immune cells using zirconium-89-labeled poly(lactic-co-glycolic acid) nanoparticles, showing potential applications in various disease models.