Page 175 - Cellular Imaging in Regenerative Medicine, Cancer and Osteoarthritis

Summary, Discussion, Concluding remarks
Macrophages constitute an important cellular component of inflammatory diseases. Upon activation macrophages can differentiate, oversimplified stated, into pro- or anti- inflammatory macrophages (64). Macrophages can change their functional phenotype during their existence; these specific functional and phenotypic properties are affected by the micro-environment (65). Their varied roles can exacerbate and/or resolve diseases. The phagocytic nature, abundance and disease homing properties of macrophages can be targeted for imaging and therapeutic purposes. The ability to image specific phenotypes (pro- and anti-inflammatory macrophages) could help to predict disease progression or assess the stage of disease and considerably contribute to current disease treatment regimens (66).
Osteoarthritis (OA) has traditionally been thought to be a purely biomechanical disease, but in recent years there has been a shift in understanding how OA originates. Now it is seen as an inflammatory disease with macrophage involvement, however it is still unclear to what extent inflammation is an initiator versus an outcome of the joint destructive process. The contributions of different phenotypes of macrophages to OA pathogenesis are currently not well understood (67). It would be favourable to non-invasively trace the presence of different phenotypes of macrophages in vivo during OA development. A way to achieve this is by SPECT imaging. In Chapter 7 we investigated the value of the somatostatin receptor subtype 2 as a novel imaging marker for pro-inflammatory macrophages also using the DMM osteoarthritic mouse model. First we evaluated gene expression levels of SST2 in unstimulated as well as in IFNγ+TNFα stimulated human macrophages by qPCR. The expression of SST2 mRNA significantly increased by a factor of 3.6 relative to that in unstimulated macrophages. A similar effect was also observed synovial tissue of OA patients. From patients with OA who got a knee resection synovial tissue was removed and stimulated in vitro with IFNγ+TNFα, resulting in a 10-fold increased expression level of SST2 mRNA relative to that in unstimulated tissue. Moreover, stimulation of primary monocyte-derived macrophages with IFNγ+TNFα in vitro resulted in a significant increase of [111In] In-DOTA-TATE uptake. To establish the relevance of SST2 tracer as a marker for pro-inflammatory macrophages in vivo, presence of macrophages and uptake of SST2 tracer was studied in a mouse DMM model for OA over time.
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