| First Author | Cao Q | Year | 2021 |
| Journal | Theranostics | Volume | 11 |
| Issue | 7 | Pages | 3527-3539 |
| PubMed ID | 33537102 | Mgi Jnum | J:337355 |
| Mgi Id | MGI:6804235 | Doi | 10.7150/thno.49421 |
| Citation | Cao Q, et al. (2021) Abraxane-induced bone marrow CD11b(+) myeloid cell depletion in tumor-bearing mice is visualized by muPET-CT with (64)Cu-labeled anti-CD11b and prevented by anti-CSF-1. Theranostics 11(7):3527-3539 |
| abstractText | To investigate the utility of noninvasive microPET-CT with (64)Cu-DOTA-anti-CD11b ((64)Cu-alphaCD11b) in assessing bone marrow status after anticancer therapies, and the protective role of anti-CSF-1 (alphaCSF-1) against bone marrow suppression induced by Abraxane. Methods: MDA-MB-435 tumor-bearing mice were treated with Abraxane, alphaCSF-1, or alphaCSF-1 plus Abraxane. microPET-CT and biodistribution of (64)Cu-alphaCD11b 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 alphaCSF-1 was investigated for its role in protecting bone marrow cells, using a transgenic mouse model that expresses functional human CSF-1. Results: muPET-CT showed that (64)Cu-alphaCD11b had high uptake in the bone marrow and spleen of both normal and tumor-bearing mice. Abraxane significantly reduced (64)Cu-alphaCD11b uptake in the bone marrow and spleen of treated mice compared to untreated mice. Interestingly, (64)Cu-alphaCD11b muPET-CT revealed that alphaCSF-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, alphaCSF-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 alphaCSF-1 also alleviated the effects of Abraxane on bone marrow cells in transgenic mice expressing human CSF-1, suggesting clinical relevance of alphaCSF-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 muPET-CT with (64)Cu-alphaCD11b and prevented by alphaCSF-1. |
