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Imaging infection still represents a challenge for researchers. Despite nuclear medicine (NM) offers valuable tools able to discriminate between infections and inflammation, there is an unmet clinical need to develop new strategies able to specifically target the causative pathogen, to select the best antimicrobial treatment for each patient and to accurately assess therapeutic efficacy. These aspects are commonly addressed by microbiology or histology but the diagnosis often relies on invasive procedures that are prone to contamination or sample bias and do not reflect the spatial heterogeneity of the infective process. Therefore, in the era of personalized medicine and treatment, a lot of efforts are in play to improve a personalized diagnosis. Molecular imaging is an ideal candidate for this purpose and, indeed, research is going fast to this direction aiming to find more selective and proper antimicrobial treatments and to overcome broad-spectrum antibiotic use, which still represents the major cause of bacterial drug-resistance. Several approaches for specifically image bacteria have been proposed and provided encouraging perspectives in preclinical studies. Nevertheless, the majority of these promising approaches are still confined in "bench stages" and crucial issues still need to be addressed before their translation in clinical practice. This review will focus on radiolabeled antibiotics for SPECT imaging of bacteria, their mechanisms of action, their potentiality and limitations for "bed-side" applications.

In the past decades, the expanding use of prostate-specific membrane antigen (PSMA) imaging for prostate cancer has led to the incidental detection of a lot of extra-prostatic malignancies showing an increased uptake of PSMA. Due to these incidental findings, the increasing amount of immunohistochemistry studies and the deeper knowledge of the mechanisms of expression of this antigen, it is now clear that “PSMA” is a misnomer, since it is not specific to the prostate gland. Nevertheless, this lack of specificity could represent an interesting opportunity to bring new insights on the biology of PSMA and its sites of expression to image and treat new conditions, particularly several cancers. In this review, we will describe the main extra-prostatic cancers that exhibit PSMA expression and that can be studied with PSMA-based positron emission tomography–computed tomography (PET/CT) as an additional or alternative tool to conventional imaging. In particular, we will focus on cancers in which a radioligand therapy with 177lutetium has been attempted, aiming to provide an overview of the possible future theragnostic applications of PSMA.

Immune system is emerging as a crucial protagonist in a huge variety of oncologic and non-oncologic conditions including response to vaccines and viral infections (such as SARS-CoV-2). The increasing knowledge of molecular biology underlying these diseases allowed the identification of specific targets and the possibility to use tailored therapies against them. Immunotherapies and vaccines are, indeed, more and more used nowadays for treating infections, cancer and autoimmune diseases and, therefore, there is the need to identify, quantify and monitor immune cell trafficking before and after treatment. This approach will provide crucial information for therapy decision-making. Imaging of B and T-lymphocytes trafficking by using tailored radiopharmaceuticals proved to be a successful nuclear medicine tool. In this review, we will provide an overview of the state of art and future trends for "in vivo" imaging of lymphocyte trafficking and homing by mean of specific receptor-tailored radiopharmaceuticals.

Purpose Consensus on optimal imaging procedure for vascular graft/endograft infection (VGEI) is still lacking and the choice of a diagnostic test is often based on the experience of single centres. This document provides evidence-based recommendations aiming at defining which imaging modality may be preferred in different clinical settings and post-surgical time window. Methods This working group includes 6 nuclear medicine physicians appointed by the European Association of Nuclear Medicine, 4 vascular surgeons, and 2 radiologists. Vascular surgeons formulated 5 clinical questions that were converted into 10 statements and addressed through a systematic analysis of available literature by using PICOs (Population/problem–Intervention/Indicator–Comparator–Outcome) strategy. Each consensus statement was scored for level of evidence and for recommendation grade, according to the Oxford Centre for Evidence-based Medicine criteria. Results Sixty-six articles, published from January 2000 up to December 2021, were analysed and used for evidence-based recommendations. Conclusion Computed tomography angiography (CTA) is the first-line imaging modality in suspected VGEI but nuclear medicine modalities are often needed to confirm or exclude the infection. Positron emission tomography/computed tomography (PET/CT) with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) has very high negative predictive value but it should be performed preferably at least 4 months after surgery to avoid false positive results. Radiolabelled white blood cell (WBC) scintigraphy, given its high diagnostic accuracy, can be performed at any time after surgery. Preamble The European Association of Nuclear Medicine (EANM) is a professional no-profit medical association that facilitates communication worldwide between individuals pursuing clinical and research excellence in nuclear medicine. The EANM was founded in 1985. EANM members are physicians, technologists, and scientists specializing in the research and practice of nuclear medicine. The EANM will periodically define new guidelines for nuclear medicine practice to help advance the science of nuclear medicine and to improve the quality of service to patients throughout the world. Existing practice guidelines will be reviewed for revision or renewal, as appropriate, on their fifth anniversary or sooner, if indicated. Each practice guideline, representing a policy statement by the EANM, has undergone a thorough consensus process in which it has been subjected to extensive review. The EANM recognizes that the safe and effective use of diagnostic nuclear medicine imaging requires specific training, skills, and techniques, as described in each document. Reproduction or modification of the published practice guideline by those entities not providing these services is not authorized. These guidelines are an educational tool designed to assist practitioners in providing appropriate care for patients. They are not inflexible rules or requirements of practice and are not intended, nor should they be used, to establish a legal standard of care. For these reasons and those set forth below, the EANM suggests caution against the use of the current consensus document in litigation in which the clinical decisions of a practitioner are called into question. The ultimate judgement regarding the propriety of any specific procedure or course of action must be made by the physician or medical physicist in the light of all the circumstances presented. Thus, there is no implication that an approach differing from the consensus document, standing alone, is below the standard of care. To the contrary, a conscientious practitioner may responsibly adopt a course of action different from that set forth in the consensus document when, in the reasonable judgement of the practitioner, such course of action is indicated by the condition of the patient, limitations of available resources, or advances in knowledge or technology subsequent to publication of the consensus document. The practice of medicine includes both the art and the science of the prevention, diagnosis, alleviation, and treatment of disease. The variety and complexity of human conditions make it impossible to always reach the most appropriate diagnosis or to predict with certainty a particular response to treatment. Therefore, it should be recognized that adherence to this consensus document will not ensure an accurate diagnosis or a successful outcome. All that should be expected is that the practitioner will follow a reasonable course of action based on current knowledge, available resources, and the needs of the patient, to deliver effective and safe medical care. The sole purpose of this consensus document is to assist practitioners in achieving this objective.

Introduction: Thyroidectomy followed by radioactive iodine therapy (RAI) is the treatment of choice for differentiated thyroid carcinoma (DTC). Serum thyroglobulin (Tg) measurement has proved to be useful for predicting persistent and/or recurrent disease during follow-up of DTC patients. In our study, we evaluated the risk of disease recurrence in patients with papillary thyroid carcinoma (PTC), who were treated with thyroidectomy and RAI, by measuring serum Tg at different time-points: at least 40 days after surgery, in euthyroidism with TSH < 1.5 and usually 30 days before RAI (Tg−30), on the day of RAI (Tg0), and seven days after RAI (Tg+7). Methods: One hundred and twenty-nine patients with PTC were enrolled in this retrospective study. All patients were treated with 131I for thyroid remnant ablation. Disease relapse (nodal disease or distant disease) during at least 36 months follow-up was evaluated by serum measurements of Tg, TSH, AbTg at different time points and by imaging techniques (neck ultrasonography, 131I-whole body scan (WBS) after Thyrogen® stimulation). Typically, patients were assessed at 3, 6, 12, 18, 24, and 36 months after RAI. We classified patients in five groups: (i) those who developed nodal disease (ND), (ii) those who developed distant disease (DD), (iii) those with biochemical indeterminate response and minimal residual thyroid tissue (R), (iv) those with no evidence of structural or biochemical disease + intermediate ATA risk (NED-I), and (v) those with no evidence of structural or biochemical disease + low ATA risk (NED-L). ROC curves for Tg were generated to find potential discriminating cutoffs of Tg values in all patients’ groups. Results: A total of 15 out of 129 patients (11.63%) developed nodal disease and 5 (3.88%) distant metastases, during the follow-up. We found that Tg−30 (with suppressed TSH) has the same sensitivity and specificity than Tg0 (with stimulated TSH), and it is slightly better than Tg+7, which can be influenced by the size of the residual thyroid tissue. Conclusion: Serum Tg−30 value, measured in euthyroidism 30 days before RAI, is a reliable prognostic factor to predict future nodal or distant disease, thus allowing to plan the most appropriate therapy and follow-up.

Aim The aim of this mini-review was to summarize the role of positron emission tomography/computed tomography (PET/CT) with 18Fluorine-fluorodeoxyglucose ([18F]FDG) in inflammatory and infective processes, based on the published scientific evidence. Methods We analysed clinical indications, patient preparation, image acquisition protocols, image interpretation, pitfalls and how to make the report of cardio-vascular diseases, musculoskeletal diseases and other inflammatory and infective systemic diseases. Results of this analysis are shown in practical tables, easy to understand for daily routine consultation. Conclusions Despite [18F]FDG is currently used in several inflammatory and infective diseases, standardized interpretation criteria are still needed in most cases. It is, therefore, foreseen the execution of multicentre clinical studies that, by adopting the same acquisition and interpretation criteria, may contribute to the standardization of this imaging modality.

Sjögren's syndrome (SS) is a progressive autoimmune disease characterized by local mononuclear cell infiltration of the salivary and lachrymal glands. Labial biopsy demonstrates local infiltration by Th1 cells that produce pro-inflammatory cytokines, such as interleukin-2 (IL2). The aim of this study was to assess the utility ofWe investigated 48 patients with primary SS and 27 control subjects using

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Background The understanding of the role of different immune cell subsets that infiltrate tumors can help researchers in developing new targeted immunotherapies to reactivate or reprogram them against cancer. In addition to conventional drugs, new cell-based therapies, like adoptive cell transfer, proved to be successful in humans. Indeed, after the approval of anti-CD19 CAR-T cell therapy, researchers are trying to extend this approach to other cancer or cell types. Main body This review focuses on the different approaches to non-invasively monitor the biodistribution, trafficking and fate of immune therapeutic cells, evaluating their efficacy at preclinical and clinical stages. PubMed and Scopus databases were searched for published articles on the imaging of cell tracking in humans and preclinical models. Conclusion Labelling specific immune cell subtypes with specific radiopharmaceuticals, contrast agents or optical probes can elucidate new biological mechanisms or predict therapeutic outcome of adoptive cell transfer therapies. To date, no technique is considered the gold standard to image immune cells in adoptive cell transfer therapies.

To investigate the cause of lymphopenia in patients with newly diagnosed COVID-19, we measured [We studied, by [Patients had moderate severity COVID-19 syndrome. Basal [These findings indicate that lymphopenia in COVID-19 patients is associated with large bowel inflammation supporting the hypothesis that CD4 + lymphocytes migrate to peripheral lymphoid tissues in the bowel.

DFIs and VGEIs represent two difficult scenarios from a diagnostic point of view and the prompt identification of the infection benefit from a multidisciplinary and multimodal approach in which NM plays a crucial role. As far as DFIs is concerned, a plethora of radiological and NM modalities are available and can be used and combined for the diagnosis, but at the moment no definite diagnostic flowchart exists (Chapter 2). In Chapter 3, MRI, 99mTc-HMPAO WBC scintigraphy and [18F]FDG PET/CT showed a comparable sensitivity in detecting pedal OM. In Chapter 4, we compared MRI, 99mTc-HMPAO WBC scintigraphy and [18F]FDG PET/CT in detecting OM, STIs and Charcot in a large population of diabetic patients.VGEI is another condition in which standardized diagnostic algorithms and a unanimous consensus on the most appropriate imaging modality are still needed. CTA, WBC scintigraphy and [18F]FDG PET/CT play a complementary role being CTA always the first-choice imaging modality (Chapter 5). From our retrospective comparative study on CTA, radiolabelled WBCs and [18F]FDG PET/CT (Chapters 6), the addition of a NM examination resulted in a better patient’s management in our population. Recently published EANM guidelines (Chapter 7) fully assessed the role of different imaging modalities in the diagnostic setting of VGEI according to time elapsed from surgery. WBC scintigraphy can be performed at any time from surgery, given its high accuracy in discriminating post-surgical inflammation from an infection. [18F]FDG PET/CT should be performed at least 4 months after surgery, given the possibility of false positive findings due to sterile inflammation.

Pancreatic neuroendocrine neoplasms (panNENs) are part of a large family of tumors arising from the neuroendocrine system. PanNENs show low–intermediate tumor grade and generally high somatostatin receptor (SSTR) expression. Therefore, panNENs benefit from functional imaging with 68Ga-somatostatin analogues (SSA) for diagnosis, staging, and treatment choice in parallel with morphological imaging. This narrative review aims to present conventional imaging techniques and new perspectives in the management of panNENs, providing the clinicians with useful insight for clinical practice. The 68Ga-SSA PET/CT is the most widely used in panNENs, not only fr diagnosis and staging purpose but also to characterize the biology of the tumor and its responsiveness to SSAs. On the contrary, the 18F-Fluordeoxiglucose (FDG) PET/CT is not employed systematically in all panNEN patients, being generally preferred in G2–G3, to predict aggressiveness and progression rate. The combination of 68Ga-SSA PET/CT and 18F-FDG PET/CT can finally suggest the best therapeutic strategy. Other radiopharmaceuticals are 68Ga-exendin-4 in case of insulinomas and 18F-dopamine (DOPA), which can be helpful in SSTR-negative tumors. New promising but still-under-investigation radiopharmaceuticals include radiolabeled SSTR antagonists and 18F-SSAs. Conventional imaging includes contrast enhanced CT and multiparametric MRI. There are now enriched by radiomics, a new non-invasive imaging approach, very promising to early predict tumor response or progression.

Objectives: Interstitial pneumonia is a severe complication induced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Several treatments have been proposed alone or, more often, in combination, depending, also, on the presence of other organ disfunction. The most frequently related, well-described, and associated phenomenon is pan-lymphopenia with circulating, high levels of cytokines. We report, here, on two patients with COVID-19 and lymphoproliferative disorders treated with Tocilizumab (a humanized monoclonal antibody against the interleukin-6 receptor) and followed by an [18F]FDG PET/CT to early evaluate the therapy’s efficacy. Methods: One patient with angioimmunoblastic T-lymphoma (A), one with Hodgkin lymphoma (A), and both with positive RT-PCR for SARS-CoV-2 and with similar clinical findings of interstitial pneumonia at the CT scan, were imaged by [18F]FDG PET/CT before and 14 days after a single dose of Tocilizumab. Results: In both patients, the basal [18F]FDG PET/CT showed a diffused lung parenchyma uptake, corresponding to the hyperdense areas at the CT scan. After 2 weeks of a Tocilizumab infusion, patient B had an improvement of symptoms, with normalization of the [18F]FDG uptake. By contrast, patient A, who was still symptomatic, showed a persisting and abnormal distribution of [18F]FDG. Interestingly, both patients showed a low bone marrow uptake of [18F]FDG at the diagnosis and after 15 days, while the spleen uptake was low only in lymphopenic patient A; both are indirect signs of an immune deficiency. Conclusions: In conclusion, in these two patients, interstitial pneumonia was efficiently treated with Tocilizumab, as demonstrated by the [18F]FDG PET/CT. Our results confirm that interleukin-6 (IL6) has a role in the COVID-19 disease and that anti-cytokine treatment can also be performed in patients with lymphoproliferative disorders.

Inflammatory musculoskeletal diseases represent a group of chronic and disabling conditions that evolve from a complex interplay between genetic and environmental factors that cause perturbations in innate and adaptive immune responses. Understanding the pathogenesis of inflammatory musculoskeletal diseases is, to a large extent, derived from preclinical and basic research experiments. In vivo molecular imaging enables us to study molecular targets and to measure biochemical processes non-invasively and longitudinally, providing information on disease processes and potential therapeutic strategies, e.g. efficacy of novel therapeutic interventions, which is of complementary value next to ex vivo (post mortem) histopathological analysis and molecular assays. Remarkably, the large body of preclinical imaging studies in inflammatory musculoskeletal disease is in contrast with the limited reports on molecular imaging in clinical practice and clinical guidelines. Therefore, in this EANM-endorsed position paper, we performed a systematic review of the preclinical studies in inflammatory musculoskeletal diseases that involve radionuclide imaging, with a detailed description of the animal models used. From these reflections, we provide recommendations on what future studies in this field should encompass to facilitate a greater impact of radionuclide imaging techniques on the translation to clinical settings. Supplementary Information The online version contains supplementary material available at (10.1186/s13550-021-00820-8).

Background: Molecular nuclear medicine, due to hybrid imaging camera systems and new tailored radiopharmaceuticals, has been gained a clinical relevance for diagnosis, therapy and follow-up of solid tumors. Despite numerous literature studies, many new radiopharmaceuticals for imaging tumor microenvironment, have not yet been used, routinely, in oncological clinical practice to monitor treatments. This is due to poor comparability of published studies, due to poor design and methodology, heterogeneous population and prevalence of preclinical studies. Methods: In this systematic review, we described the use of radiopharmaceuticals for evaluation of tumor treatment response by targeting microenvironment. We reviewed studies published from 2000 to 2020, to provide an updated status of research in this topic. Results: There is a growing role of radiopharmaceuticals and nuclear medicine imaging techniques in the management of cancer treatments, especially immunotherapy. Of the 24 papers included, 16 were preclinical studies. Conclusions: New radiopharmaceuticals could have an excellent impact in molecular imaging, leading to better diagnosis and important clinical information for therapy decision making and follow-up of cancer treatments in different solid tumors. Recently developed radiopharmaceuticals may provide great advantage to improve personalized medicine for patients with a great cost-effectiveness ratio.

Aim The diagnosis, severity and extent of a sterile inflammation or a septic infection could be challenging since there is not one single test able to achieve an accurate diagnosis. The clinical use of 18F-fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) imaging in the assessment of inflammation and infection is increasing worldwide. The purpose of this paper is to achieve an Italian consensus document on [18F]FDG PET/CT or PET/MRI in inflammatory and infectious diseases, such as osteomyelitis (OM), prosthetic joint infections (PJI), infective endocarditis (IE), prosthetic valve endocarditis (PVE), cardiac implantable electronic device infections (CIEDI), systemic and cardiac sarcoidosis (SS/CS), diabetic foot (DF), fungal infections (FI), tuberculosis (TBC), fever and inflammation of unknown origin (FUO/IUO), pediatric infections (PI), inflammatory bowel diseases (IBD), spine infections (SI), vascular graft infections (VGI), large vessel vasculitis (LVV), retroperitoneal fibrosis (RF) and COVID-19 infections. Methods In September 2020, the inflammatory and infectious diseases focus group (IIFG) of the Italian Association of Nuclear Medicine (AIMN) proposed to realize a procedural paper about the clinical applications of [18F]FDG PET/CT or PET/MRI in inflammatory and infectious diseases. The project was carried out thanks to the collaboration of 13 Italian nuclear medicine centers, with a consolidate experience in this field. With the endorsement of AIMN, IIFG contacted each center, and the pediatric diseases focus group (PDFC). IIFG provided for each team involved, a draft with essential information regarding the execution of [18F]FDG PET/CT or PET/MRI scan (i.e., indications, patient preparation, standard or specific acquisition modalities, interpretation criteria, reporting methods, pitfalls and artifacts), by limiting the literature research to the last 20 years. Moreover, some clinical cases were required from each center, to underline the teaching points. Time for the collection of each report was from October to December 2020. Results Overall, we summarized 291 scientific papers and guidelines published between 1998 and 2021. Papers were divided in several sub-topics and summarized in the following paragraphs: clinical indications, image interpretation criteria, future perspectivess and new trends (for each single disease), while patient preparation, image acquisition, possible pitfalls and reporting modalities were described afterwards. Moreover, a specific section was dedicated to pediatric and PET/MRI indications. A collection of images was described for each indication. Conclusions Currently, [18F]FDG PET/CT in oncology is globally accepted and standardized in main diagnostic algorithms for neoplasms. In recent years, the ever-closer collaboration among different European associations has tried to overcome the absence of a standardization also in the field of inflammation and infections. The collaboration of several nuclear medicine centers with a long experience in this field, as well as among different AIMN focus groups represents a further attempt in this direction. We hope that this document will be the basis for a “common nuclear physicians’ language” throughout all the country. Supplementary Information The online version contains supplementary material available at 10.1007/s40336-021-00445-w.

Differentiated thyroid cancer (DTC) cells may lose NIS expression and iodine uptake, but usually express TSH receptors (TSHR). Therefore, the aim of our study was to compare two radiolabeled superagonist TSH analogues for DTC imaging. These analogues (namely TR1401 and TR1402) have a higher TSHR binding affinity than recombinant human TSH (Thyrogen®). Radiolabeling was performed with technetium-99m using an indirect method via HYNIC conjugation and was followed by in vitro quality controls and binding assay on TSHR-positive cell lines (ML-1). An in vitro binding assay was also performed and compared with radiolabeled human recombinant TSH. In vivo imaging was performed in four dogs with spontaneous follicular thyroid carcinoma with solid poorly differentiated areas with 99mTc-TR1401 SPECT/CT, 99mTc-TR1402 SPECT/CT, and [18F]FDG PET/CT on different days within 2 weeks. TR1401 and TR1402 were labeled with high specific activity (8.3 ± 1.2 MBq/µg) and retention of their biological activity and structural integrity. Both agonists were able to efficiently bind TSHR receptors expressed by cell lines with dissociation constants (Kd) of 2.7 nM for 99mTc-TR1401 and 0.5 nM for 99mTc-TR1402 compared with 99mTc-Thyrogen (Kd = 8.4 nM). In tumor-targeting experiments, a focal uptake was observed in dogs with spontaneous intraglandular thyroid carcinoma, in which TSHR expression was confirmed by immunohistochemistry. 99mTc-TR1402 provided higher T/B than 99mTc-TR1401 and [18F]FDG (12.9 ± 1.3, 10.2 ± 0.7, and 3.8 ± 0.6, respectively, all p &lt, 0.001). Given these results, 99mTc-TR1402 appears to be a useful tool for in vivo imaging of thyroid cancer.

Despite the application of EANM recommendations for radiolabelled white-blood-cells (WBC) scintigraphy, some cases still remain doubtful based only on visual analysis. The aim of this study was to investigate the role of semi-quantitative analysis and bone marrow scan (BMS) in solving doubtful cases. We retrospectively evaluated all [99mTc]HMPAO-WBC scintigraphies performed, in the last 7 years, for a suspected monolateral prosthetic joint infection (PJI). In doubtful cases, we used five different thresholds of increase of target-to-background (T/B) ratio, between delayed and late images, as criteria of positivity (5%, 10%, 15%, 20% and 30%). BMS were also analysed and sensitivity, specificity and accuracy of different methods were calculated according to final diagnosis. The sensitivity, specificity and accuracy were, respectively, 77.8%, 43.8% and 53.0% for the cut-off at 5%, 72.2%, 66.7% and 68.2% for the cut-off at 10%, 66.7%, 75.0% and 72.7% for the cut-off at 15%, 66.7%, 85.4% and 80.3% for the cut-off at 20%, 33.3%, 93.8% and 77.3% for the cut-off at 30%. BMS provided a significantly higher diagnostic performance than 5%, 10% and 15% thresholds. Conversely, we did not observe any statistically significant difference between BMS and the cut-off of more than 20%. Therefore, doubtful cases should be analysed semi-quantitatively. An increase in T/B ratio of more than 20% between delayed and late images, should be considered as a criterion of positivity, thus avoiding BMS.

INTRODUCTION Nuclear medicine plays a crucial role for personalized therapy, mainly in oncology. Chemotherapy and radiotherapy present some disadvantages and research is shifting toward nanotechnology with significant improvements in therapy and diagnosis of several cancers. Indeed, nanoparticles can be tagged with different radioisotopes for single photon emission computed tomography (SPECT) and positron emission tomography (PET) imaging and for therapy. This review describes the current state of the art of 64Copper-labeled nanoparticles for PET imaging of cancer. EVIDENCE ACQUISITION We performed a systematic analysis of literature using the terms "64CuCl 2 ," "64Cu," "Copper" AND "nanoparticle" AND "PET" in online databases: i.e. PubMed/MEDLINE and Scopus. The search was limited to English papers and original articles. We excluded articles not in English language, abstracts, case reports, review articles and meeting presentations. EVIDENCE SYNTHESIS Amongst the 116 articles retrieved, 88 were excluded because reviews, or not in English, or only in-vitro studies or meeting presentations. We considered only 28 original papers. The most used nanoparticles are liposomes and they are mainly used in breast cancer although other animal models of cancer have been also investigated. CONCLUSIONS The results showed that nanoparticles can be considered a promising radiopharmaceutical for PET imaging of different type of cancer.

Diabetic foot infections (DFIs) are severe complications of long-standing diabetes, and they represent a diagnostic challenge, since the differentiation between osteomyelitis (OM), soft tissue infection (STI), and Charcot’s osteoarthropathy is very difficult to achieve. Nevertheless, such differential diagnosis is mandatory in order to plan the most appropriate treatment for the patient. The isolation of the pathogen from bone or soft tissues is still the gold standard for diagnosis; however, it would be desirable to have a non-invasive test that is able to detect, localize, and evaluate the extent of the infection with high accuracy. A multidisciplinary approach is the key for the correct management of diabetic patients dealing with infective complications, but at the moment, no definite diagnostic flow charts still exist. This review aims at providing an overview on multimodality imaging for the diagnosis of DFI and to address evidence-based answers to the clinicians when they appeal to radiologists or nuclear medicine (NM) physicians for studying their patients.

Molecular medicine has gained clinical relevance for the detection and staging of oncological diseases, to guide therapy decision making and for therapy follow-up due to the availability of new highly sensitive hybrid imaging camera systems and the development of new tailored radiopharmaceuticals that target specific molecules. The knowledge of the expression of different receptors on the primary tumor and on metastases is important for both therapeutic and prognostic purposes and several approaches are available aiming to achieve personalized medicine in different oncological diseases. In this review, we describe the use of specific radiopharmaceuticals to image and predict therapy response in breast cancer and neuroendocrine tumors since they represent a paradigmatic example of the importance of tumoral characterization of hormonal receptors in order to plan a tailored treatment. The most attractive radiopharmaceuticals for breast cancer are 16α-[18F]-fluoro-17β-estradiol for PET assessment of the estrogen expression, radiolabeled monoclonal antibody trastuzumab to image the human epidermal growth factor receptor 2, but also the imaging of androgen receptors with [18F]-fluorodihydrotestosterone.

Vascular graft infection (VGI) is a rare but severe complication of vascular surgery that is associated with a bad prognosis and high mortality rate. An accurate and prompt identification of the infection and its extent is crucial for the correct management of the patient. However, standardized diagnostic algorithms and a univocal consensus on the best strategy to reach a diagnosis still do not exist. This review aims to summarize different radiological and Nuclear Medicine (NM) modalities commonly adopted for the imaging of VGI. Moreover, we attempt to provide evidence-based answers to several practical questions raised by clinicians and surgeons when they approach imaging in order to plan the most appropriate radiological or NM examination for their patients.

Diabetic foot infections (DFIs) represent one of the most frequent and disabling morbidities of longstanding diabetes, therefore, early diagnosis is mandatory. The aim of this multicenter retrospective study was to compare the diagnostic accuracy of white blood cell scintigraphy (WBC), 18F-fluorodeoxyglucose positron emission tomography/computed tomography ((18F) FDG PET/CT), and Magnetic Resonance Imaging (MRI) in patients with suspected DFI. Images and clinical data from 251 patients enrolled by five centers were collected in order to calculate the sensitivity, specificity, and accuracy of WBC, FDG, and MRI in diagnosing osteomyelitis (OM), soft-tissue infection (STI), and Charcot osteoarthropathy. In OM, WBC acquired following the European Society of Nuclear Medicine (EANM) guidelines was more specific and accurate than MRI (91.9% vs. 70.7%, p &lt, 0.0001 and 86.2% vs. 67.1%, p = 0.003, respectively). In STI, both FDG and WBC achieved a significantly higher specificity than MRI (97.9% and 95.7% vs. 83.6%, p = 0.04 and p = 0.018, respectively). In Charcot, both MRI and WBC demonstrated a significantly higher specificity and accuracy than FDG (88.2% and 89.3% vs. 62.5%, p = 0.0009, 80.3% and 87.9% vs. 62.1%, p &lt, 0.02, respectively). Moreover, in Charcot, WBC was more specific than MRI (89.3% vs. 88.2% p &lt, 0.0001). Given the limitations of a retrospective study, WBC using EANM guidelines was shown to be the most reliable imaging modality to differentiate between OM, STI, and Charcot in patients with suspected DFI.

Infective endocarditis (IE) is a serious cardiac condition, which includes a wide range of clinical presentations, with varying degrees of severity. The diagnosis is multifactorial and a proper characterization of disease requires the identification of the primary site of infection (usually the cardiac valve) and the search of secondary systemic complications. Early depiction of local complications or distant embolization has a great impact on patient management and prognosis, as it may induce to aggressive antibiotic treatment or, in more advanced cases, cardiac surgery. In this setting, the multimodality imaging has assumed a pivotal role in the clinical decision making and it requires the physician to be aware of the advantages and disadvantages of each imaging technique. Echocardiography is the first imaging test, but it has several limitations. Therefore, the integration with other imaging modalities (computed tomography, magnetic resonance imaging, nuclear imaging) becomes often necessary. Different strategies should be applied depending on whether the infection is suspected or already ascertained, whether located in native or prosthetic valves, in the left or right chambers, or if it involves an implanted cardiac device. In addition, detection of extracardiac IE-related lesions is crucial for a correct management and treatment. The aim of this review is to illustrate strengths and weaknesses of the various methods in the most common clinical scenarios.

In the field of inflammation imaging, nuclear medicine techniques can be considered as a non-invasive tool to early detect pathophysiological changes in affected tissues. These changes usually occur before clinical onset of symptoms and before the development of anatomical changes, that are commonly detected by radiological procedures. This is particularly important for prognostic purposes, therapy decision making and for therapy follow-up. Here we review the current state-of-the art of nuclear medicine for diagnostic purposes in different conditions characterized by a chronic inflammation, such as vulnerable atherosclerotic plaques, vasculitis, rheumatoid arthritis, Sjogren syndrome, autoimmune thyroid diseases, inflammatory bowel diseases, Coeliac disease, Type 1 diabetes mellitus and other immunological diseases. Overall, we describe several different approaches based on radiolabeled cells, peptides and antibodies or FDG. It emerges the role of PET and of hybrid cameras in particular (SPECT/CT and PET/CT) for diagnosis of these disorders and for therapy decision making and followup.