Page 176 - Cellular Imaging in Regenerative Medicine, Cancer and Osteoarthritis

Chapter 8
DMM and sham knees were histologically stained for CD64. The number of CD64 positive cells, indicating pro-inflammatory macrophages, was elevated at day 1 and 3, and slowly diminished during the following weeks. With SPECT, increased amounts of radioactivity were found in the knees, during the first 7 days after DMM surgery followed by a gradual decrease over time. Herein we saw a similar pattern for both the knees in which OA was induced by DMM and for the knees that underwent sham surgery. As shown in this study, the influx of macrophages was time dependent and associated with the development path of OA. Influx of macrophages was also observed in the sham-operated knee, most likely due to the inflammatory reaction to tissue damage caused by surgical manipulation. It should be noted that the sham knees had no structural cartilage damage or osteophyte formation. Synovium consists of a heterogeneous cell population including synoviocytes, macrophages and fibroblasts. Although it cannot fully be excluded that SST2 tracer is taken up by cells other than macrophages, we consider this option highly unlikely to substantially contribute to the measured activity.
As said before, macrophages play a role in many different diseases, like also in inflammation of an atherosclerotic plaque. In the clinic different pilot studies have been performed with an SST2 tracer to image atherosclerotic inflammation (68-70). These studies found that 68Ga-DOTA-TATE PET enables measurement of generalized atherosclerotic disease activity and offers detailed information about local plaque functional phenotype. Imaging with 68Ga-DOTA-TATE has therefore the potential to improve cardiovascular disease risk prediction. Despite we used an animal model resulting in only mild inflammation, we were already able to successfully visualize, quantify and monitor the inflammation process by SPECT/CT imaging. These findings are promising for the use of SST2 targeting tracers in studying macrophage involvement in several disease processes. Macrophages are crucial in the development and progression of various diseases, so accurate imaging of pro-inflammatory macrophages, beside anti-inflammatory macrophages, might be an important step forward in understanding disease development.
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