Evaluation of a radiolabeled somatostatin analog for SPECT imaging of pro-inflammatory macrophages

Background: Macrophages are crucial in the development and progression of various diseases. To monitor their role, various proteins expressed by macrophages may be used as imaging target. In this preclinical study we investigate the value of the somatostatin receptor subtype 2 (SSTR2) as a novel imaging marker for proinflammatory macrophages, using an experimental osteoarthritis (OA) mouse model. Methods: SSTR2 gene expression levels in pro-inflammatory macrophages and human synovium was determined by qPCR. Tracer binding was determined in macrophages and human osteoarthritic synovium after in vitro stimulation with IFNγ and TNFα. Presence of pro-inflammatory macrophages in OA mice was determined by anti-CD64+ staining. Accumulation of the tracer in OA knees was determined by μSPECT. Results: Human macrophages and synovial tissue stimulated with IFNγ+TNFα had significantly upregulated SSTR2 gene expression and showed increased uptake of SSTR2-targeting tracer. Shortly after OA induction an increase in the presence of pro-inflammatory macrophages was seen as assessed by immunohitochemsitry. Similar findings were obtained with SPECT, with peak uptake of the SSTR2-targeting tracer immediately after surgery followed by a gradual decrease during the course of the next 8 weeks. Conclusions: Pro-inflammatory macrophages have elevated SSTR2 expression which makes it possible to image an inflammatory process in the knee with a radiolabeled somatostatin analog for SPECT.