Page 159 - Cellular Imaging in Regenerative Medicine, Cancer and Osteoarthritis

SPECT imaging of pro-inflammatory macrophages
in the knee, and the pattern seen with the presence of pro-inflammatory macrophages (histological aCD64 staining) of the knee, proceeded in the same way; starting with an high influx of macrophages which decreased during the course of time.
For potential clinical relevance we evaluated SSTR2 tracer uptake in synovial tissue samples derived from OA patients. OA synovium showed specific uptake of [111In]In-DOTA-JR11, which could be further enhanced under acutely induced inflammatory conditions (stimulation with IFNγ+TNFα). There was considerable variation in uptake of the SSTR2 tracer between patient samples which was most likely due to the large heterogeneity in disease state between OA patients and whether or not a given patient had a flare of inflammation at time of surgery. It is also known that synovium consists of a heterogeneous cell population including synoviocytes, macrophages and fibroblasts. Although it cannot fully be excluded that SSTR2-binding tracer is taken up by cells other than macrophages, we consider this option highly unlikely to substantially contribute to the measured activity. It is known that the number of macrophages dramatically increases in inflammatory arthritis relative to healthy synovia (41, 42), also seen in this study using histological evaluation. It is therefore most likely that the signal in inflamed knees is caused by the presence of pro-inflammatory macrophages.
In this research high resolution scans are of utmost importance, because the target is very small. That is why we used an indium-111 labeled tracer. When this tracer is going to be used in the clinic we will be using a radioactive isotope compatible with PET. PET has in the clinic a higher resolution, half-life of radioactive isotopes is shorter so patients can leave the hospital sooner and images are less noisy therefor accurate quantification can be performed.
We made use of a mouse model where we introduced OA through destabilization of the medial meniscus. Mice knees are very small and DMM results in a mild inflammation. Altough we had these restrictions we were able to successfully visualize, quantify and monitor the inflammation process by SPECT/CT imaging. Perhaps with the use of a larger animal model and/or a disease model with more macrophage involvement, like rheumatoid arthritis (43, 44), will facilitate further research. Our findings are promising for the use
157
7