Introduction: Hybrid [¹⁸F]FDG PET imaging is currently the method of choice for a wide variety of infectious and inflammatory disorders and was recently adopted in several clinical guidelines. A large amount of evidence-based articles, guidelines and appropriate use criteria have been published since the first version of this guideline in 2013. Purpose: To provide updated evidence-based information to assist physicians in recommending, performing and interpreting hybrid [¹⁸F]FDG PET examinations for infectious and inflammatory disorders in the adult population. Methods: A systematic literature search of evidence-based articles using whole-body [¹⁸F]FDG hybrid imaging on the indications covered within this guideline was performed. All systematic reviews and meta-analyses published within the last 10 years until January 2023 were identified in PubMed/Medline or Cochrane. For each indication covered in this manuscript, diagnostic performance was provided based on meta-analyses or systematic reviews. If not available, results from prospective or retrospective studies were considered based on predefined selection criteria. Results and conclusions: Hybrid [¹⁸F]FDG PET is extremely useful in the work-up and management of adults with infectious and inflammatory diseases, as supported by extensive and rapidly growing evidence-based literature and adoption in clinical guidelines. Practical recommendations are provided describing evidence-based indications as well as interpretation criteria and pitfalls. Monitoring treatment response is the most challenging but insufficiently studied potential application in infection and inflammation imaging.

Purpose: Patients with fever and inflammation of unknown origin (FUO/IUO) are clinically challenging due to variable clinical presentations with nonspecific symptoms and many differential diagnoses. Positron emission tomography/computed tomography (PET/CT) with 2-deoxy-2-[¹⁸F]fluoro-D-glucose ([¹⁸F]FDG) is increasingly used in FUO and IUO, but the optimal diagnostic strategy remains controversial. This consensus document aims to assist clinicians and nuclear medicine specialists in the appropriate use of [¹⁸F]FDG-PET/CT in FUO and IUO based on current evidence. Methods: A working group created by the EANM infection and inflammation committee performed a systematic literature search based on PICOs with “patients with FUO/IUO” as population, “[¹⁸F]FDG-PET/CT” as intervention, and several outcomes including pre-scan characteristics, scan protocol, diagnostic yield, impact on management, prognosis, and cost-effectiveness. Results: We included 68 articles published from 2001 to 2023: 9 systematic reviews, 49 original papers on general adult populations, and 10 original papers on specific populations. All papers were analysed and included in the evidence-based recommendations. Conclusion: FUO and IUO remains a clinical challenge and [¹⁸F]FDG PET/CT has a definite role in the diagnostic pathway with an overall diagnostic yield or helpfulness in 50–60% of patients. A positive scan is often contributory by directly guiding treatment or subsequent diagnostic procedure. However, a negative scan may be equally important by excluding focal disease and predicting a favorable prognosis. Similar results are obtained in specific populations such as ICU-patients, children and HIV-patients.

Diagnosing a peri-prosthetic joint infection (PJI) remains challenging despite the availability of a variety of clinical signs, serum and synovial markers, imaging techniques, microbiological and histological findings. Moreover, the one and only true definition of PJI does not exist, which is reflected by the existence of at least six different definitions by independent societies. These definitions are composed of major and minor criteria for defining a PJI, but most of them do not include imaging techniques. This paper highlights the pros and cons of available imaging techniques—X-ray, ultrasound, computed tomography (CT), Magnetic Resonance Imaging (MRI), bone scintigraphy, white blood cell scintigraphy (WBC), anti-granulocyte scintigraphy, and fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT), discusses the added value of hybrid camera systems—single photon emission tomography/computed tomography (SPECT/CT), PET/CT and PET/MRI and reports consensus answers on important clinical questions that were discussed during the Third European Congress on Inflammation/Infection Imaging in Rome, December 2019.

The low abundance of Hodgkin/Reed-Sternberg (HRS) cells in lymph node biopsies in classical Hodgkin lymphoma (cHL) complicates the analysis of somatic genetic alterations in HRS cells. As circulating cell-free DNA (cfDNA) contains circulating tumor DNA (ctDNA) from HRS cells, we prospectively collected cfDNA from 177 patients with newly diagnosed, mostly early-stage cHL in a monocentric study at Leuven, Belgium (n = 59) and the multicentric BREACH study by Lymphoma Study Association (n = 118). To catalog the patterns and frequencies of genomic copy number aberrations (CNAs), cfDNA was sequenced at low coverage (0.26×), and data were analyzed with ichorCNA to yield read depth-based copy number profiles and estimated clonal fractions in cfDNA. At diagnosis, the cfDNA concentration, estimated clonal fraction, and ctDNA concentration were significantly higher in cHL cases than controls. More than 90% of patients exhibited CNAs in cfDNA. The most frequent gains encompassed 2p16 (69%), 5p14 (50%), 12q13 (50%), 9p24 (50%), 5q (44%), 17q (43%), 2q (41%). Losses mostly affected 13q (57%), 6q25-q27 (55%), 4q35 (50%), 11q23 (44%), 8p21 (43%). In addition, we identified loss of 3p13-p26 and of 12q21-q24 and gain of 15q21-q26 as novel recurrent CNAs in cHL. At diagnosis, ctDNA concentration was associated with advanced disease, male sex, extensive nodal disease, elevated erythrocyte sedimentation rate, metabolic tumor volume, and HRS cell burden. CNAs and ctDNA rapidly diminished upon treatment initiation, and persistence of CNAs was associated with increased probability of relapse. This study endorses the development of ctDNA as gateway to the HRS genome and substrate for early disease response evaluation.

The role of fibroblast activation protein inhibitor (FAPI) positron emission tomography/computed tomography (PET/CT) is emerging for the assessment of non-oncological diseases, such as inflammatory and infectious diseases, even if the evidence in the literature is still in its initial phases. We conducted a systematic search of Scopus, PubMed/MEDLINE, Embase, and Cochrane library databases for studies published before 31 December 2023 reporting infectious and inflammatory disease imaging with FAPI PET/CT. We included twenty-one studies for a total of 1046 patients. The most frequent disease studied was lung interstitial disease, investigated in six studies for a total of 200 patients, followed by bone and joint diseases in two studies and 185 patients, IgG4-related disease in 53 patients, and Crohn’s disease in 30 patients. Despite the heterogeneity of studies in terms of study design and technical features, FAPI PET/CT showed a high detection rate and diagnostic role. Moreover, when compared with 2-[¹⁸F]FDG PET/CT (n = 7 studies), FAPI PET/CT seems to have better diagnostic performances. The presence of chronic inflammation and tissue remodeling, typical of immune-mediated inflammatory conditions, may be the underlying mechanism of FAPI uptake.

Allogeneic cardiac-derived progenitor cells (CPC) without immunosuppression could provide an effective ancillary therapy to improve cardiac function in reperfused myocardial infarction. We set out to perform a comprehensive preclinical feasibility and safety evaluation of porcine CPC (pCPC) in the infarcted porcine model, analyzing biodistribution and mid-term efficacy, as well as safety in healthy non-infarcted swine. The expression profile of several pCPC isolates was compared with humans using both FACS and RT-qPCR. ELISA was used to compare the functional secretome. One week after infarction, female swine received an intracoronary (IC) infusion of vehicle (CON), 25 × 106 pCPC (25 M), or 50 × 106 pCPC (50 M). Animals were followed up for 10 weeks using serial cardiac magnetic resonance imaging to assess functional and structural remodeling (left ventricular ejection fraction (LVEF), systolic and diastolic volumes, and myocardial salvage index). Statistical comparisons were performed using Kruskal-Wallis and Mann-Whitney U tests. Biodistribution analysis of 18F-FDG-labeled pCPC was also performed 4 h after infarction in a different subset of animals. Phenotypic and functional characterization of pCPC revealed a gene expression profile comparable to their human counterparts as well as preliminary functional equivalence. Left ventricular functional and structural remodeling showed significantly increased LVEF 10 weeks after IC administration of 50 M pCPC, associated to the recovery of left ventricular volumes that returned to pre-infarction values (LVEF at 10 weeks was 42.1 ± 10.0% in CON, 46.5 ± 7.4% in 25 M, and 50.2 ± 4.9% in 50 M, p < 0.05). Infarct remodeling was also improved following pCPC infusion with a significantly higher myocardial salvage index in both treated groups (0.35 ± 0.20 in CON; 0.61 ± 0.20, p = 0.04, in 25 M; and 0.63 ± 0.17, p = 0.01, in 50 M). Biodistribution studies demonstrated cardiac tropism 4 h after IC administration, with substantial myocardial retention of pCPC-associated tracer activity (18% of labeled cells in the heart), and no obstruction of coronary flow, indicating their suitability as a cell therapy product. IC administration of allogeneic pCPC at 1 week after acute myocardial infarction is feasible, safe, and associated with marked structural and functional benefit. The robust cardiac tropism of pCPC and the paracrine effects on left ventricle post-infarction remodeling established the preclinical bases for the CAREMI clinical trial (NCT02439398).