Michel Eisenblaetter MD, Presenter: Nothing to Disclose

Thomas Vogl PhD, Abstract Co-Author: Nothing to Disclose

Christoph B. Bremer MD, Abstract Co-Author: Nothing to Disclose

Tumor associated macrophages (TAM) have been shown to substantially promote local tumor progression, e.g. by facilitating basement-membrane breakdown. TAM density and activity correlates with poor prognosis in malignant disease. The local expression of S100A9 is strictly dependant on macrophage activity. This study should confirm the possibility to visualise TAM activity, reflected by S100A9 expression in tumor models using Optical Imaging (OI), driven by a S100A9-specific probe and moreover to assess whether this in-vivo imaging approach is capable of determination of the malignant potential of tumor lesions.  

An antibody, addressing S100A9, was labelled with Cy5.5 for in-vivo OI. Labelled IGG (Cy5.5 for single or Cy7 for parallel inj.) served as control for unspecific tracer distribution. Balb/c mice were inoculated with 4T1 murine breast cancer or MOS murine osteosarcoma and the tumor size was determined daily. OI was performed tumor size dependant 24h after injection of the fluorescence probes (single or parallel injection). For correlation of imaging results, immunohistochemistry of tumor sections was performed and tumor cells were analysed for S100A9 expression using ELISA.  

Neither 4T1 nor MOS cells showed significant S100A9 production in ELISA. In fast-growing 4T1 tumors, Anti-S100A9-Cy5.5 injection resulted in fluorescence signal which was regularly about two-fold higher compared to IGG-Cy5.5 (2432.5 vs. 1244.6; p<0.005). At same size, slow-growing MOS accumulated less Anti-S100A9-Cy5.5 than 4T1 (1678.3 vs. 2432.5), reflecting lower macrophage activity. Histology confirmed in-vivo imaging results regarding TAM density. Initially measured S100A9-signals proved to predict the growth rate of 4T1 tumors (1638.9 – 27% growth over 10d; 2842 – 68%; R2=0.85). Parallel injection of Anti-S100A9-Cy5.5 and IGG-Cy7 did not alter the acquired fluorescence signals compared to single injection of the tracers, screening out significant in-vivo competition for the target structure.  

S100A9-specific OI allows for in-vivo visualisation of TAM activity in primary tumor lesions and therefore for the estimation of their malignant potential.

Imaging of tumor associated macrophages proved to have a predictive value for tumor growth and will moreover increase understanding of their role in tumor biology and thus influence tumor treatment.

Eisenblaetter, M, Vogl, T, Bremer, C, In Vivo Assessment of the Malignant Potential of Tumor Lesions Using Macrophage-specific Optical Imaging.  Radiological Society of North America 2011 Scientific Assembly and Annual Meeting, November 26 - December 2, 2011 ,Chicago IL. http://archive.rsna.org/2011/11011614.html