Page 158 - Cellular Imaging in Regenerative Medicine, Cancer and Osteoarthritis

Chapter 7
Discussion
Pro-inflammatory macrophages have been identified as crucial mediators in various disease processes. Non-invasive monitoring of their presence during disease progression is therefore very desirable. In this report, we showed that pro-inflammatory macrophages (IFNγ+TNFα stimulated) had elevated SSTR2 expression and showed concomitant increased uptake of SSTR2-targeting radiolabeled peptides, which are suitable as SPECT tracers. Using such a SSTR2 SPECT tracer in a translational setting, we also demonstrated that under pro- inflammatory conditions there was increased binding of the tracer in human OA synovium. Moreover, in an in vivo model we showed that macrophage- associated inflammation resulted in concomitant uptake of [111In]In-DTPA- octreotide in mouse knees, indicating that an SSTR2-targeting SPECT tracer can be used to monitor the course of a pro-inflammatory response over time in vivo.
Destabilization of the medial meniscus in mice was used as a model for OA with anticipated involvement of pro-inflammatory macrophages. In many other studies this model has been used for studying processes during the onset of OA and in studies evaluating novel intervention strategies for OA (37-39). This animal model has a low variability (31) and represents posttraumatic human injury which leads to joint degeneration (40). During human OA development a macrophage influx was seen (41) and macrophage-associated inflammation was related with structural damage and disease progression.
As shown in this study, it appeared that the influx of macrophages was time dependent and associated with the development path of OA, but the macrophage influx in the knee was not exclusively associated with development of OA. An 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, features that are associated with OA. Since the SSTR2 tracer specifically targets inflammatory cells, and not damaged cartilage, SSTR2 receptor uptake occured in both DMM and sham-operated knees due to the presence of inflammatory macrophages in both situations. The pattern seen with uptake of SSTR2 targeting tracer
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