FDG-PET, combined with CT, is nowadays getting more and more relevant for the diagnosis of several infectious and inflammatory diseases and particularly for therapy monitoring. Thus, this paper gives special attention to the role of FDG-PET/CT in the diagnosis and therapy monitoring of infectious and inflammatory diseases. Enough evidence in the literature already exists about the usefulness of FDG-PET/CT in the diagnosis, management, and followup of patients with sarcoidosis, spondylodiscitis, and vasculitis. For other diseases, such as inflammatory bowel diseases, rheumatoid arthritis, autoimmune pancreatitis, and fungal infections, hard evidence is lacking, but studies also point out that FDG-PET/CT could be useful. It is of invaluable importance to have large prospective multicenter studies in this field to provide clear answers, not only for the status of nuclear medicine in general but also to reduce high costs of treatment.

Tumor-infiltrating immune cells play a key role against cancer. However, malignant cells are able to evade the immune response and establish a very complex balance in which different immune subtypes may drive tumor progression, metastatization and resistance to therapy. New immunotherapeutic approaches aim at restoring the natural balance and increase immune response against cancer by different mechanisms. The complexity of these interactions and the heterogeneity of immune cell subpopulations are a real challenge when trying to develop new immunotherapeutics and evaluate or predict their efficacy in vivo. To this purpose, molecular imaging can offer non-invasive diagnostic tools like radiopharmaceuticals, contrast agents or fluorescent dyes. These agents can be useful for preclinical and clinical purposes and can overcome [ 18 F]FDG limitations in discriminating between trueprogression and pseudo-progression. This review provides a comprehensive overview of immune cells involved in microenvironment, available immunotherapies and imaging agents to highlight the importance of new therapeutic biomarkers and their in vivo evaluation to improve the management of cancer patients.

There has been a significant increase in the number of joint prosthesis replacements worldwide. Although relatively uncommon, complications can occur with the most serious being an infection. Various radiological and nuclear imaging techniques are available to diagnose prosthetic joint infections (PJI). In this review article, we describe the pathophysiology of PJI, the principles of nuclear medicine imaging and the differences between Single Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET). The value of nuclear medicine techniques for clinical practice is also discussed.Then we provide an overview of the most often used radionuclide imaging techniques that may be helpful in diagnosing prosthetic joint infection: the 67 Ga-citrate, labelled white blood cells in vitro and in vivo (monoclonal antibodies directed against specific targets on the leukocytes), and 18 F-fluorodeoxyglucose ( 18 F-FDG). We describe their working methods, the pitfalls, and the interpretation criteria. Furthermore, we review recent advances in imaging bacteria, a molecular imaging method that holds promises for the detection of occult infections. We conclude proposing two diagnostic flow-charts, based on data in the literature, that could help the clinicians to choose the best nuclear imaging method when they have a patient with suspicion of or with proven PJI.

Using this protocol, visual analysis had high sensitivity and specificity in the diagnosis of infection. Semiquantitative analysis could be used in doubtful cases, with no cut-off for the percentage increase in radiolabelled WBC over time, as a criterion to define a positive scan.

Bacterial infections are still one of the main causes of patient morbidity and mortality worldwide. Nowadays, many imaging techniques, like computed tomography or magnetic resonance imaging, are used to identify inflammatory processes, but, although they recognize anatomical modifications, they cannot easily distinguish bacterial infective foci from non bacterial infections. In nuclear medicine, many efforts have been made to develop specific radiopharmaceuticals to discriminate infection from sterile inflammation. Several compounds (antimicrobial peptides, leukocytes, cytokines, antibiotics…) have been radiolabelled and tested in vitro and in vivo, but none proved to be highly specific for bacteria. Indeed factors, including the number and strain of bacteria, the infection site, and the host condition may affect the specificity of tested radiopharmaceuticals. Ciprofloxacin has been proposed and intensively studied because of its easy radiolabelling method, broad spectrum, and low cost, but at the same time it presents some problems such as low stability or the risk of antibiotic resistance. Therefore, in the present review studies with ciprofloxacin and other radiolabelled antibiotics as possible substitutes of ciprofloxacin are reported. Among them we can distinguish different classes, such as cephalosporins, fluoroquinolones, inhibitors of nucleic acid synthesis, inhibitors of bacterial cell wall synthesis and inhibitors of protein synthesis; then also others, like siderophores or maltodextrin-based probes, have been discussed as bacterial infection imaging agents. A systematic analysis was performed to report the main characteristics and differences of each antibiotic to provide an overview about the state of the art of imaging infection with radiolabelled antibiotics.

Background: Bacterial infections are still one of the main factors associated with mortality worldwide. Many radiopharmaceuticals were developed for bacterial imaging, both with single photon emission computed tomography (SPECT) and positron emission tomography (PET) isotopes. This review focuses on PET radiopharmaceuticals, performing a systematic literature review of published studies between 2005 and 2018. Methods: A systematic review of published studies between 2005 and 2018 was performed. A team of reviewers independently screened for eligible studies. Because of differences between studies, we pooled the data where possible, otherwise, we described separately. Quality of evidence was assessed by Quality Assessment of Diagnostic Accuracy Studies (QUADAS) approach. Results: Eligible papers included 35 published studies. Because of the heterogeneity of animal models and bacterial strains, we classified studies in relation to the type of bacterium: Gram-positive, Gram-negative, Gram-positive and negative, others. Conclusions: Results highlighted the availability of many promising PET radiopharmaceuticals for bacterial imaging, despite some bias related to animal selection and index test, but few have been translated to human subjects. Results showed a lack of standardized infection models and experimental settings.

Early in the course of immunotherapy there is frequently a transient enlargement of tumor masses (pseudo-progression) due to tumor infiltration by TILs. Current clinical imaging modalities are not able to distinguished pseudo-progression from true tumor progression. Thus, patients often remain on treatment 4-8 weeks longer to confirm disease progression. Nuclear medicine offers the possibility to image immune cells and potentially discriminate pseudo-progression and progression.We conducted a pilot study in patients with metastatic melanoma receiving ipilimumab (IPI) or pembrolizumab (PEMBRO) to assess safety and feasibility of SPECT/CT imaging with 99mTc- interleukin-2 (99mTc-HYNIC-IL2) to detect TILs and distinguish between true progression from pseudo- progression. Scans were performed prior to and after 12w treatment. After labelling,99mTc-HYNIC-IL2 was purified and diluted in 10 mL of 5% glucose with 0.1% human serum albumin.Of the 5 patients (2 treated with IPI and 3 with PEMBRO) enrolled, two failed to complete the second scan as they discontinued IPI due grade 3 colitis (1 patient) or patient refusal after developing multiple toxicities attributed to IPI (1 patient). Following the first scan, one patient reported to have a grade 1 pruritus with grade 1 pain. No other toxicities attributed to the radiopharmaceutical infusion were reported. Metastatic lesions could be visualized by 99mTc-IL2 imaging and there was positive correlation between size and 99mTc-HYNIC-IL2 uptake, both before and after 12 weeks of therapy.The results of this pilot study demonstrate the safety and feasibility of 99mTc-IL2 imaging and has led to a number of hypotheses to be tested in future studies.

These in vivo and ex vivo studies confirm the specificity of (99m)Tc-HYNIC-IL-2 for imaging activated T lymphocytes in carotid plaques. (99m)Tc-HYNIC-IL-2 is a true marker for the inflamed plaque and therefore of plaque instability.