Early diagnosis of colorectal cancer by CD11b+ myeloid-derived suppressor cells imaging

Objectives It is well known that inflammatory bowel disease is tightly correlated to the inflammation associated colonic carcinogenesis. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population includes myeloid progenitors and immature myeloid cells (IMCs)that play criticle role in the immuno-escape of multiple tumors. Herein, this study is intended to develop 99mTc labeled anti-CD11b antibody for colorectal cancer early diagnosis.

Methods Orthotopic colorectal cancer animal model was created by intraperitoneal injection of the azoxymethane(AOM) to histamine deficient HDC knockout (HDC-/-) mice and plus feeding mice with dextran sodium sulfate (DSS) in drinking water. Anti-CD11b antibody was conjugated with MAG3 and labeled with 99mTc. Both HDC-/- mice and normal C57 mice were received 1 mCi of 9mTc-anti-CD11b antibody, and micro-SPECT/CT scannings were performed 6 h post injection. After imaging, the mice were sacrificed, blood and colon was collected. Then flow cytometry analysis of mobilization of CD11b+Gr-1+ medullary system immune cells from peripheral circulation blood was done. Also, anti-CD11b immunofluorescence staining was performed to identify infiltration of CD11b+ immune cells in microenvironment of colonic neoplasms.

Results Small in situ colonic neoplasma (around 3 mm diameter) was clearly visible in 99mTc-anti-CD11b SPECT/CT images. In vitro FACS analysis and anti-CD11b immunofluorescence staining confrimed CD11b+Gr-1+MDSCs are more abundant in peripheral circulation blood model mice and matrices of tumor comparing to C57 mice.

Conclusions Targeted microenviroment imaging strategy could be facilitated to tumor early diagnosis, and isotope labeled anti-CD-11b is worthwhile further evaluation as a potential probe.