Monitoring chemotherapy-induced bone marrow toxicity and the potential protective effect of anti-CSF-1 using microPET/CT with 64Cu-DOTA-anti-CD11b

Objectives Bone marrow suppression is a common side effect of chemo- and radiotherapy. In many cases, the dose of chemotherapy or radiotherapy-induced bone marrow toxicity can be better estimated by accurately measure the change of bone marrow cell population. The objective of this study was to assess and quantify the response of bone marrow to chemotherapy.

Methods Anti-CD11b was labeled with 64Cu via DOTA chelator. Cell uptake of 64Cu-DOTA-anti-CD11b was performed using bone marrow cells obtained from normal mice with or without exposure to Abraxane. microPET-CT imaging and biodistribution were performed after intravenous injection of 64Cu-DOTA-anti-CD11b in nude mice bearing subcutaneously inoculated MDA-MB-435 breast tumors. Tumor-bearing mice were divided into 3 groups: no treatment control, Abraxane treatment alone, and combined anti-mouse CSF-1 antibody and Abraxane treatments.

Results In vitro, the uptake of 64Cu-DOTA-anti-CD11b in marrow-derived myeloid cells was directly related to the viability of these cells. PET-CT imaging showed that 64Cu-DOTA-anti-CD11b had high uptake in the bone marrow and spleen of tumor-bearing mice. Abraxane treatment caused significant reduction in the uptake of 64Cu-DOTA-anti-CD11b in the bone marrow and spleen compared to non-treatment control. Interestingly, combining anti-CSF-1 with Abraxane alleviated the depletion effect of Abraxane on bone marrow cell population.

Conclusions 64Cu-DOTA-anti-CD11b may be a useful PET imaging agent for monitor bone marrow toxicity. Moreover, anti-CSF-1 may have potential protective function for chemotherapy-induced bone marrow toxicity.