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.
| Original language | English |
|---|---|
| Pages (from-to) | 433-436 |
| Number of pages | 4 |
| Journal | Journal of Nuclear Medicine |
| Volume | 61 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 1 Mar 2020 |
Funding
This work was supported by the MSK Molecularly Targeted Intraoperative Imaging Fund, the Tow foundation, and National Institutes of Health grants R35 CA232130, R01 CA204441, P30 CA008748, R01 CA220234, and F32-EB025050. No other potential conflict of interest relevant to this article was reported.
| Funders | Funder number |
|---|---|
| National Institutes of Health | R01 CA220234 |
| National Cancer Institute | R35CA232130, P30CA008748, R01CA204441 |
| National Institute of Biomedical Imaging and Bioengineering | F32EB025050 |
Keywords
- CSF1R inhibitor
- HDL
- immunotherapy
- PET/CT imaging
- tumor-associated macrophages