Journal
JOURNAL OF NUCLEAR MEDICINE
Volume 61, Issue 3, Pages 433-436Publisher
SOC NUCLEAR MEDICINE INC
DOI: 10.2967/jnumed.119.230466
Keywords
immunotherapy; tumor-associated macrophages; PET/CT imaging; CSF1R inhibitor; HDL
Funding
- MSK Molecularly Targeted Intraoperative Imaging Fund
- Tow foundation
- National Institutes of Health [R35 CA232130, R01 CA204441, P30 CA008748, R01 CA220234, F32-EB025050]
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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 Zr-89-labeled high-density lipoprotein (Zr-89-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 Zr-89-HDL within the tumor was assessed using PET/CT imaging and autoradiography, whereas TAM burden was determined using immunofluorescence. Results: A significant reduction in Zr-89-HDL accumulation was observed in PET/CT images, with 2.9% +/- 0.3% and 3.7% +/- 0.2% injected dose/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 Zr-89-HDL nanoparticles as a PET tracer to quickly monitor the response to CSF1R inhibitors and other therapeutic strategies targeting TAMs.
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