An 89Zr-HDL PET Tracer Monitors Response to a CSF1R Inhibitor. Academic Article uri icon

Overview

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.

publication date

  • August 16, 2019

Research

keywords

  • Lipoproteins, HDL
  • Positron Emission Tomography Computed Tomography
  • Radioisotopes
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
  • Zirconium

Identity

PubMed Central ID

  • PMC7067531

Scopus Document Identifier

  • 85078339426

Digital Object Identifier (DOI)

  • 10.2967/jnumed.119.230466

PubMed ID

  • 31420495

Additional Document Info

volume

  • 61

issue

  • 3