An (89)Zr-HDL PET tracer monitors response to a CSF1R inhibitor Journal Article


Authors: Mason, C. A.; Kossatz, S.; Carter, L. M.; Pirovano, G.; Brand, C.; Guru, N.; PĂ©rez-Medina, C.; Lewis, J. S.; Mulder, W. J. M.; Reiner, T.
Article Title: An (89)Zr-HDL PET tracer monitors response to a CSF1R inhibitor
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 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.
Keywords: inhibitor; immunotherapy; pet/ct imaging; breast-cancer; criteria; tumor-associated macrophages; hdl; csf1r
Journal Title: Journal of Nuclear Medicine
Volume: 61
Issue: 3
ISSN: 0161-5505
Publisher: Society of Nuclear Medicine  
Date Published: 2020-03-01
Start Page: 433
End Page: 436
Language: English
ACCESSION: WOS:000518436700026
DOI: 10.2967/jnumed.119.230466
PROVIDER: wos
PMCID: PMC7067531
PUBMED: 31420495
Notes: Article -- Source: Wos
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MSK Authors
  1. Jason S Lewis
    305 Lewis
  2. Thomas Reiner
    99 Reiner
  3. Christian Brand
    23 Brand
  4. Susanne   Kossatz
    35 Kossatz
  5. Lukas M Carter
    19 Carter
  6. Christian A Mason
    4 Mason
  7. Navjot Guru
    5 Guru