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- Title
In Vivo PET Imaging of Monocytes Labeled with [ 89 Zr]Zr-PLGA-NH 2 Nanoparticles in Tumor and Staphylococcus aureus Infection Models.
- Authors
Krekorian, Massis; Cortenbach, Kimberley R. G.; Boswinkel, Milou; Kip, Annemarie; Franssen, Gerben M.; Veltien, Andor; Scheenen, Tom W. J.; Raavé, René; van Riessen, Nicolaas Koen; Srinivas, Mangala; de Vries, Ingrid Jolanda M.; Figdor, Carl G.; Aarntzen, Erik H. J. G.; Heskamp, Sandra
- Abstract
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. 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.
- Subjects
IN vivo studies; MOLECULAR diagnosis; ANIMAL experimentation; RADIOISOTOPES; MAGNETIC resonance imaging; STAPHYLOCOCCAL diseases; DIAGNOSTIC imaging; SINGLE-photon emission computed tomography; TUMORS; MONOCYTES; NANOPARTICLES; MICE
- Publication
Cancers, 2021, Vol 13, Issue 20, p5069
- ISSN
2072-6694
- Publication type
Article
- DOI
10.3390/cancers13205069