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

To investigate the utility of noninvasive mu PET-CT with Cu-64-DOTA-anti-CD11b (Cu-64-aCD11b) in assessing bone marrow status after anticancer therapies, and the protective role of anti-CSF-1 (alpha CSF-1) against bone marrow suppression induced by Abraxane. Methods: MDA-MB-435 tumor-bearing mice were treated with Abraxane, alpha CSF-1, or alpha CSF-1 plus Abraxane. mu PET-CT and biodistribution of Cu-64-alpha 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 alpha CSF-1 was investigated for its role in protecting bone marrow cells, using a transgenic mouse model that expresses functional human CSF-1. Results: mu PET-CT showed that Cu-64-alpha CD11b had high uptake in the bone marrow and spleen of both normal and tumor-bearing mice. Abraxane significantly reduced Cu-64-alpha CD11b uptake in the bone marrow and spleen of treated mice compared to untreated mice. Interestingly, Cu-64-alpha CD11b pPET-CT revealed that alpha 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, alpha 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 alpha CSF-1 also alleviated the effects of Abraxane on bone marrow cells in transgenic mice expressing human CSF-1, suggesting clinical relevance of alpha 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 pPET-CT with Cu-64-alpha CD11b and prevented by alpha CSF-1.

Automated summary

The study investigated the utility of noninvasive mu PET-CT with Cu-64-DOTA-anti-CD11b in assessing bone marrow status after anticancer therapies and the protective role of anti-CSF-1 against bone marrow suppression induced by Abraxane. The results showed high uptake of Cu-64-alpha CD11b in the bone marrow and spleen of mice, with Abraxane reducing uptake in treated mice and alpha CSF-1 alleviating the depletion of bone marrow cells caused by Abraxane. These findings suggest a potential clinical relevance of alpha CSF-1 in preventing bone marrow suppression.