A Comprehensive Review of SSTR-Based Spect and Pet Imaging in Chronic Inflammatory and Immune-Mediated Diseases

Abstract

Background: Somatostatin receptors (SSTRs), especially subtype 2 (SSTR2), are increasingly recognized as valuable molecular targets in the imaging of chronic inflammatory and immune-mediated diseases. Their expression on activated immune and stromal cells enables specific, non-invasive detection of inflammatory activity using radio-labeled somatostatin analogs. Objective: This review aims to summarize current evidence on SSTR-targeted imaging across a range of chronic inflammatory and immune-mediated diseases, compare its diagnostic value with 18F-FDG PET/CT, and discuss biological mechanisms, clinical applications, and remaining challenges. Methods: A literature-based narrative review was conducted, integrating preclinical studies, clinical trials, and comparative imaging research involving SSTR PET/SPECT tracers such as 68Ga-DOTATATE, 68Ga-DOTANOC, 99ᵐTc-HYNIC-TOC, and 111In-pentetreotide in diseases including vasculitis, sarcoidosis, autoimmune myocarditis, rheumatoid arthritis, and thyroid-associated ophthalmopathy. Results: SSTR-targeted imaging has shown promising specificity for inflammatory lesions and provides favorable lesion-to-background contrast, particularly in tissues with high physiological FDG uptake such as the myocardium and brain. In vasculitis and sarcoidosis, SSTR-targeted tracers may complement FDG PET by improving diagnostic confidence and inter-observer consistency in selected small studies. Mechanistically, SSTR2 expression is closely associated with cytokine-driven immune activation, predominantly involving M1 macrophages. However, current evidence remains limited by heterogeneous receptor expression, variable myocardial uptake, and the lack of standardized imaging protocols. Conclusions: SSTR-targeted molecular imaging represents a biologically grounded and clinically promising complementary approach for assessing immune-mediated inflammation. Future developments in tracer design, quantitative standardization, and multicenter clinical validation are warranted to establish its role in precision diagnostics.