Abstract
The immune function within the tumor microenvironment has become a prominent therapeutic target, with tumor-associated macrophages (TAMS) playing a critical role in immune suppression. We propose an 89Zr-labeled high-density lipoprotein (89Zr-HDL) nanotracer as a means of monitoring response to immunotherapy. Methods: Female MMTV-PyMT mice were treated with pexidartinib, a colony-stimulating factor 1 receptor (CSF1R) inhibitor, to reduce TAM density. The accumulation of 89Zr-HDL within the tumor was assessed using PET/CT imaging and autoradiograpy, whereas TAM burden was determined using immunofluorescence. Results: A significant reduction in 89Zr-HDL accumulation was observed in PET/CT images, with 2.9 ± 0.3 %ID/g and 3.7 ± 0.2 %ID/g for the pexidartinib- and vehicle-treated mice, respectively. This reduction was corroborated ex vivo and correlated with decreased TAM density. Conclusion: These results support the potential use of 89Zr-HDL nanoparticles as a PET tracer that could quickly monitor the response to CSF1R inhibitors and other therapeutic strategies targeting TAMs.
- Animal Imaging
- Breast
- Correlative Imaging
- CSF1R inhibitor
- HDL
- Immunotherapy
- PET/CT imaging
- tumor-associated macrophages
Footnotes
Immediate Open Access: Creative Commons Attribution 4.0 International License (CC BY) allows users to share and adapt with attribution, excluding materials credited to previous publications. License: https://creativecommons.org/licenses/by/4.0/. Details: http://jnm.snmjournals.org/site/misc/permission.xhtml.
- Copyright © 2019 by the Society of Nuclear Medicine and Molecular Imaging, Inc.