An <sup>89</sup>Zr-HDL PET Tracer Monitors Response to a CSF1R Inhibitor.

Mason, Christian A; Kossatz, Susanne; Carter, Lukas M; Pirovano, Giacomo; Brand, Christian; Guru, Navjot; Pérez-Medina, Carlos; Lewis, Jason S et al. · J Nucl Med · 2020

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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 <sup>89</sup>Zr-labeled high-density lipoprotein (<sup>89</sup>Zr-HDL) nanotracer as a means of monitoring response to immunotherapy. <b>Methods:</b> Female MMTV-PyMT mice were treated with pexidartinib, a colony-stimulating factor 1 receptor (CSF1R) inhibitor, to reduce TAM density. The accumulation of <sup>89</sup>Zr-HDL within the tumor was assessed using PET/CT imaging and autoradiography, whereas TAM burden was determined using immunofluorescence. <b>Results:</b> A significant reduction in <sup>89</sup>Zr-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 <i>ex vivo</i> and correlated with decreased TAM density. <b>Conclusion:</b> These results support the potential use of <sup>89</sup>Zr-HDL nanoparticles as a PET tracer to quickly monitor the response to CSF1R inhibitors and other therapeutic strategies targeting TAMs.

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