Abraxane-induced bone marrow CD11b+ myeloid cell depletion in tumor-bearing mice is visualized by ?PET-CT with 64Cu-labeled anti-CD11b and prevented by anti-CSF-1.
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ABSTRACT: To investigate the utility of noninvasive µPET-CT with 64Cu-DOTA-anti-CD11b (64Cu-?CD11b) in assessing bone marrow status after anticancer therapies, and the protective role of anti-CSF-1 (?CSF-1) against bone marrow suppression induced by Abraxane. Methods: MDA-MB-435 tumor-bearing mice were treated with Abraxane, ?CSF-1, or ?CSF-1 plus Abraxane. µPET-CT and biodistribution of 64Cu-?CD11b 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 ?CSF-1 was investigated for its role in protecting bone marrow cells, using a transgenic mouse model that expresses functional human CSF-1. Results: ?PET-CT showed that 64Cu-?CD11b had high uptake in the bone marrow and spleen of both normal and tumor-bearing mice. Abraxane significantly reduced 64Cu-?CD11b uptake in the bone marrow and spleen of treated mice compared to untreated mice. Interestingly, 64Cu-?CD11b ?PET-CT revealed that ?CSF-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, ?CSF-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 ?CSF-1 also alleviated the effects of Abraxane on bone marrow cells in transgenic mice expressing human CSF-1, suggesting clinical relevance of ?CSF-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 ?PET-CT with 64Cu-?CD11b and prevented by ?CSF-1.
SUBMITTER: Cao Q
PROVIDER: S-EPMC7847669 | biostudies-literature | 2021
REPOSITORIES: biostudies-literature
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