In Vivo PET Imaging of Monocytes Labeled with [⁸⁹Zr]Zr-PLGA-NH₂ Nanoparticles in Tumor and Staphylococcus aureus 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. ¹¹¹In-labeled poly(lactic-co-glycolic acid) with a primary amine endcap nanoparticles ([¹¹¹In]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 ⁸⁹Zr-labeled NPs for ex vivo cell labeling and in vivo cell tracking, using PET/MRI. We intrinsically and efficiently labeled PLGA-NH₂ NPs with [⁸⁹Zr]ZrCl₄. In vitro, [⁸⁹Zr]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/10⁶ cells). PET/MRI imaging could detect low numbers of [⁸⁹Zr]Zr-THP-1 cells (10,000 and 100,000 cells) injected subcutaneously in Matrigel. Last, in vivo tracking of the [⁸⁹Zr]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 [⁸⁹Zr]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.