Theranostics 2021; 11(7):3527-3539. doi:10.7150/thno.49421

Research Paper

Abraxane-induced bone marrow CD11b+ myeloid cell depletion in tumor-bearing mice is visualized by μPET-CT with 64Cu-labeled anti-CD11b and prevented by anti-CSF-1

Qizhen Cao1, Qian Huang1, Y. Alan Wang2, Chun Li1✉

1. Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77054
2. Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77054

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Citation:
Cao Q, Huang Q, Wang YA, Li C. Abraxane-induced bone marrow CD11b+ myeloid cell depletion in tumor-bearing mice is visualized by μPET-CT with 64Cu-labeled anti-CD11b and prevented by anti-CSF-1. Theranostics 2021; 11(7):3527-3539. doi:10.7150/thno.49421. Available from https://www.thno.org/v11p3527.htm

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Abstract

To investigate the utility of noninvasive µPET-CT with 64Cu-DOTA-anti-CD11b (64Cu-αCD11b) in assessing bone marrow status after anticancer therapies, and the protective role of anti-CSF-1 (αCSF-1) against bone marrow suppression induced by Abraxane.

Methods: MDA-MB-435 tumor-bearing mice were treated with Abraxane, αCSF-1, or αCSF-1 plus Abraxane. µPET-CT and biodistribution of 64Cu-αCD11b were performed after intravenous injection of the radiotracer. Cells from mouse bone marrow and MDA-MB-435 tumor were analyzed by flow cytometry. A humanized αCSF-1 was investigated for its role in protecting bone marrow cells, using a transgenic mouse model that expresses functional human CSF-1.

Results: μPET-CT showed that 64Cu-αCD11b had high uptake in the bone marrow and spleen of both normal and tumor-bearing mice. Abraxane significantly reduced 64Cu-αCD11b uptake in the bone marrow and spleen of treated mice compared to untreated mice. Interestingly, 64Cu-αCD11b μPET-CT revealed that αCSF-1 alleviated the depletion of bone marrow cells by Abraxane. These changes in the bone marrow population of CD11b+ myeloid cells were confirmed by flow cytometry. Moreover, αCSF-1 potently enhanced tolerance of bone marrow granulocytic myeloid cells to Abraxane, decreased cell migration, and suppressed recruitment of myeloid cells to the tumor microenvironment. The humanized αCSF-1 also alleviated the effects of Abraxane on bone marrow cells in transgenic mice expressing human CSF-1, suggesting clinical relevance of αCSF-1 in prevention of bone marrow suppression in addition to its role in reducing tumor-infiltrating myeloid cells.

Conclusions: Abraxane-induced bone marrow CD11b+ myeloid cell depletion in tumor-bearing mice could be noninvasively assessed by μPET-CT with 64Cu-αCD11b and prevented by αCSF-1.

Keywords: anti-CD11b, μPET-CT imaging, anti-CSF-1, Abraxane, bone marrow toxicity