An 89Zr-HDL PET Tracer Monitors Response to a CSF1R Inhibitor

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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 autoradiography, 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% 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 89Zr-HDL nanoparticles as a PET tracer to quickly monitor the response to CSF1R inhibitors and other therapeutic strategies targeting TAMs.

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Mason, C. A., Kossatz, S., Carter, L. M., Pirovano, G., Brand, C., Guru, N., … Reiner, T. (2020). An 89Zr-HDL PET Tracer Monitors Response to a CSF1R Inhibitor. Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine, 61(3), 433–436. https://doi.org/10.2967/jnumed.119.230466

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