PT  - JOURNAL ARTICLE
AU  - Christian A. Mason
AU  - Susanne Kossatz
AU  - Lukas M. Carter
AU  - Giacomo Pirovano
AU  - Christian Brand
AU  - Navjot Guru
AU  - Carlos Pérez-Medina
AU  - Jason S. Lewis
AU  - Willem J.M. Mulder
AU  - Thomas Reiner
TI  - An <sup>89</sup>Zr-HDL PET Tracer Monitors Response to a CSF1R Inhibitor
AID  - 10.2967/jnumed.119.230466
DP  - 2020 Mar 01
TA  - Journal of Nuclear Medicine
PG  - 433--436
VI  - 61
IP  - 3
4099  - http://jnm.snmjournals.org/content/61/3/433.short
4100  - http://jnm.snmjournals.org/content/61/3/433.full
SO  - J Nucl Med2020 Mar 01; 61
AB  - 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.