To review the literature on the clinical application of radiolabeled somatostatin receptor scintigraphy (SRS) by SPECT and PET in adults with chronic inflammatory diseases.

Background: Molecular nuclear medicine plays a pivotal role for diagnosis in a preclinical phase, in genetically susceptible patients, for radio-guided surgery, for disease relapse evaluation, and for therapy decision-making and follow-up. This is possible thanks to the development of new radiopharmaceuticals to target specific biomarkers of infection, inflammation and tumour immunology. Methods: In this review, we describe the use of specific radiopharmaceuticals for infectious and inflammatory diseases with the aim of fast and accurate diagnosis and treatment follow-up. Furthermore, we focus on specific oncological indications with an emphasis on tumour immunology and visualizing the tumour environment. Results: Molecular nuclear medicine imaging techniques get a foothold in the diagnosis of a variety of infectious and inflammatory diseases, such as bacterial and fungal infections, rheumatoid arthritis, and large vessel vasculitis, but also for treatment response in cancer immunotherapy. Conclusion: Several specific radiopharmaceuticals can be used to improve diagnosis and staging, but also for therapy decision-making and follow-up in infectious, inflammatory and oncological diseases where immune cells are involved. The identification of these cell subpopulations by nuclear medicine techniques would provide personalized medicine for these patients, avoiding side effects and improving therapeutic approaches.

Objectives: Primary Sjögren syndrome (SS) is diagnosed based on the American European Consensus Group (AECG) criteria, but lacks specificity, not only in the involvement of salivary glands, but also in extra-glandular involvement. Whole-body somatostatin receptor scintigraphy with ^99mTc-HYNIC-TOC scintigraphy could overcome these limitations. The aims of this study were to evaluate salivary gland uptake of ^99mTc-HYNIC-TOC in untreated patients with de-novo diagnosis of SS as compared to control subjects and as compared to conventional sialoscintigraphy with ^99mTcO₄⁻. We also aimed to evaluate the involvement of joints. Methods: ^99mTc-HYNIC-TOC was used with SS patients and uptake in joints and salivary glands was analyzed semi-quantitatively. Patients also underwent ^99mTcO₄ sialoscintigraphy. The control group that we analyzed consisted of 30 patients with neuroendocrine tumors. Results: Fifty-two females and 10 males fully met the AECG criteria for SS, and were included. A target background ratio (TBR) >1.18 in submandibular glands correctly classified 93% of the patients with SS in comparison to 27% for ^99mTcO₄ sialoscintigraphy. The area under the curve (ROC) analysis for TBR in submandibular glands was 0.95. In joints there was a huge variety in uptake. The median TBR was significantly higher in salivary glands in patients with SS compared to controls. Conclusions: ^99mTc-HYNIC-TOC scintigraphy identified active inflammatory processes not only in the salivary glands, but, unexpectedly, also in many joints in patients with primary SS, contrary to popular belief. This technique provides an objective parameter to evaluate the inflammation burden in salivary glands and joints and could be used to evaluate response to treatment.

Purpose: The aim of this systematic review was to present the current evidence on the clinical use of single-photon emission computed tomography/computed tomography (SPECT/CT) in the evaluation of noninfected painful knees after knee arthroplasty. Methods: Embase, PubMed, Google Scholar, Ovid, Scopus, Science Direct and the Cochrane Database of Systematic Reviews were searched from database inception to May 2022 following the PRISMA guidelines. As a primary outcome, we defined the role of SPECT/CT in the diagnostic approach to noninfected painful knee arthroplasty; as a secondary objective, we described the noninfection-related factors linked to painful knee arthroplasty. Pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio values and other indicators were calculated; receiver operating characteristic (ROC) curve analysis results and a summary of the areas under the curve (AUCs) from the included studies were reported. A Fagan plot, likelihood ratio plot and Deeks’ funnel plot were generated and analysed. Methodological quality was assessed using the QUADAS-2 tool, and the certainty of evidence was assessed by the GRADE approach. Results: A total of 493 publications were identified, of which eight met the inclusion criteria, with a final pooled sample size of 308 patients. The pooled sensitivity and specificity of SPECT/CT in diagnosing the source of pain in painful knee prostheses were 0.86 (95% CI: 0.75–0.93) and 0.90 (95% CI: 0.79–0.96), respectively, with pooled +LR and −LR values of 8.9 (95% CI: 4.11–19.19) and 0.15 (95% CI: 0.09–0.28). The pooled diagnostic odds ratio was 57.35, and the area under the curve was 0.94. SPECT/CT highly accurately identified different sources of pain, such as loosening of the prosthetic components, patellofemoral overloading, instability, malalignment of the components and degeneration of the patellofemoral compartment. The confidence of the estimates was moderate according to the GRADE approach. Conclusion: With demonstrated high sensitivity and specificity, as a diagnostic tool, SPECT/CT can identify the source of pain in painful knees after knee arthroplasty, particularly in cases of loosening, patellofemoral disorders and component malalignment (level of evidence III). These findings have significant clinical repercussions, such as in changing the initial diagnosis, identifying or excluding different causes of painful knee arthroplasties, guiding subsequent treatment and positively impacting the final clinical outcome. We moderately recommend the use of SPECT/CT for identifying the source of pain after knee arthroplasty according to the GRADE assessment. This review was preregistered in Prospero under code CRD42022320457.

In the last years, new insights into the molecular basis of rheumatic conditions have been described, which have generated particular interest in understanding the pathophysiology of these diseases, in which lies the explanation of the diversity of clinical presentation and the difficulty in diagnostic and therapeutic approaches. In this review, we focus on the new pathophysiological findings for Sjögren syndrome and on the derived new SPECT and PET radiopharmaceuticals to detect inflammation of immunological origin, focusing on their role in diagnosis, prognosis, and the evaluation of therapeutic efficacy.

Atherosclerosis is responsible for the majority of heart attacks and is characterized by several modifications of the arterial wall including an inflammatory reaction. The silent course of atherosclerosis has made it necessary to develop predictors of disease complications before symptomatic lesions occur. Vulnerable to rupture atherosclerotic plaques are the target for molecular imaging. To this aim, different radiopharmaceuticals for PET/CT have emerged for the identification of high-risk plaques, with high specificity for the identification of the cellular components and pathophysiological status of plaques. By targeting specific receptors on activated macrophages in high-risk plaques, radiolabelled somatostatin analogues such as ⁶⁸Ga-DOTA-TOC, TATE,0 or NOC have shown high relevance to detect vulnerable, atherosclerotic plaques. This PET radiopharmaceutical has been tested in several pre-clinical and clinical studies, as reviewed here, showing an important correlation with other risk factors.