EANM consensus document on the use of [18F]FDG PET/CT in fever and inflammation of unknown origin.

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.

The diagnostic accuracy and clinical impact of FDG-PET/CT follow-up for patients on adjuvant immunotherapy for high-risk malignant melanoma.

OBJECTIVE: The benefit of FDG-PET/CT in follow-up of patients treated with adjuvant immunotherapy after resection of high-risk malignant melanoma (MM) is debated. This study evaluated the diagnostic accuracy and clinical impact of FDG-PET/CT for diagnosing MM recurrence during the first year after surgery. METHODS: We retrospectively included 124 patients with resected high-risk MM, who received adjuvant immunotherapy and follow-up FDG-PET/CT. Clinical information and AJCC-8 stage was obtained from patients' medical records. Recurrence was verified by biopsy/progression on a subsequent scan leading to change of treatment. Non-recurrence was assumed when no metastases were observed until the subsequent follow-up scan. Incidence of recurrence, sensitivity, specificity, positive and negative predictive values (PPV and NPV) were outcome measures. RESULTS: Incidence rate of MM recurrence was 0.27 [95% CI 0.17-0.37] per person-year during the first-year. Recurrence was detected in 13 patients (10%) at 3-month FDG-PET/CT, in 10 patients (8.1%) at 6 months, 1 patient (0.8%) at 9 months, 3 patients (2.4%) at 12 months. The overall sensitivity, specificity, PPV, and NPV were 97% [86-99], 82% [78-86], 39% [29-50], and 99% [98-99], respectively. The PPV trended towards higher values as disease stage increased. At the 3-month scan, the majority of actions derived from positive findings were surgery or earlier expedition of the subsequent follow-up scan. CONCLUSION: The high rate of recurrence in patients with high-risk MM treated with adjuvant immunotherapy emphasizes the need for follow-up. The potential harm by a moderately low specificity reflecting a high number of false-positive results must be weighed against the benefit of early detection of recurrence.

A systematic literature review and meta-analysis of spectral CT compared to scintigraphy in the diagnosis of acute and chronic pulmonary embolisms.

PURPOSE: To examine the diagnostic accuracy of spectral CT pulmonary angiography (S-CTPA) using ventilation-perfusions lung scintigraphy (V/Q-scan) as a reference standard in the diagnosis of acute or chronic pulmonary embolism (APE/CPE) and chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: PubMed, Embase, Scopus, and Web of Science were searched for the period from 1 Jan 2006 to 7 Feb 2019; eligible studies had > 10 patients over 18 years old, a diagnostic outcome of PE or CTEPH, and used V/Q scan as a reference standard. Bias and applicability were assessed using QUADAS-2 tools. Sensitivities, specificities, and predictive values were noted or calculated from available information. Meta-analysis employed a fixed-effects model of Mantel and Haenszel. Heterogeneity was assessed with I-squared statistics. RESULTS: Four hundred ninety-three unique records were identified. Following screening by title, 53 studies were included in the abstract and full-text assessment. A total of six articles were included; four were suitable for a meta-analysis. Pooled sensitivity was 94.2% (95% CI, 88.3-100%), pooled specificity was 88.5% (95% CI, 81.3-95.6%), and positive and negative predictive values were 87.8% (95% CI, 80.3-95.4%) and 94.5% (95% CI, 89.3-99.7%), respectively. CONCLUSION: Data on S-CTPA for PE/CTEPH remains promising, but limited; only small studies with methodological issues are available. Evidence is best for CPE/CTEPH whereas no firm conclusions are possible for APE. There is a need for larger, prospective studies with a robust composite reference standard including state-of-the-art CTPA and V/Q-scans. KEY POINTS: • S-CTPA has high sensitivity and specificity for perfusion defects in patients with PE or CPETH. • Methodological issues and diversity of reference standards were found in the small number of included studies. • There is a need for larger prospective studies with more robust composite reference standards.

Clinical value of FDG-PET/CT in bacteremia of unknown origin with catalase-negative gram-positive cocci or Staphylococcus aureus.

INTRODUCTION: Bacteremia is associated with high mortality, especially when the site of infection is unknown. While conventional imaging usually focus on specific body parts, FDG-PET/CT visualizes hypermetabolic foci throughout the body. PURPOSE: To investigate the ability of FDG/PET-CT to detect the site of infection and its clinical impact in bacteremia of unknown origin with catalase-negative Gram-positive cocci (excluding pneumococci and enterococci) or Staphylococcus aureus (BUOCSA). METHODS: We retrospectively identified 157 patients with 165 episodes of BUOCSA, who subsequently underwent FDG-PET/CT. Data were collected from medical records. Decision regarding important sites of infection in patients with bacteremia was based on the entire patient course and served as reference diagnosis for comparison with FDG-PET/CT findings. FDG-PET/CT was considered to have high clinical impact if it correctly revealed site(s) of infection in areas not assessed by other imaging modalities or if other imaging modalities were negative/equivocal in these areas, or if it established a new clinically relevant diagnosis, and/or led to change in antimicrobial treatment. RESULTS: FDG-PET/CT detected sites of infection in 56.4% of cases and had high clinical impact in 47.3%. It was the first imaging modality to identify sites of infection in 41.1% bacteremia cases, led to change of antimicrobial therapy in 14.7%, and established a new diagnosis unrelated to bacteremia in 9.8%. Detection rate and clinical impact were not significantly influenced by duration of antimicrobial treatment preceding FDG-PET/CT, days from suspicion of bacteremia to FDG-PET/CT-scan, type of bacteremia, or cancer. CONCLUSION: FDG-PET/CT appears clinically useful in BUOCSA. Prospective studies are warranted for confirmation.

The impact of endoscopic ultrasound-guided fine-needle aspiration of lymph nodes on subsequent positron emission tomography/computed tomography imaging: a prospective study.

BACKGROUND: Modern cancer diagnostic work-up is based on multiple modalities within a short time period. The interplay between these modalities is complex and not well known. Performing biopsy procedures prior to (18)F-2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) is considered to pose a risk of false-positive imaging results; however, this is not based on solid scientific evidence. The use of endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) is commonly used in upper gastrointestinal malignancies, is proven safe, and has very little risk of complications. This study aimed to assess whether EUS-FNA induces inflammation that would increase FDG uptake on subsequent PET/CT. METHODS: 27 patients who were referred for upper gastrointestinal EUS for different reasons initially underwent FDG-PET/CT to detect biopsy-eligible lymph nodes with no FDG uptake. Patients then underwent EUS-FNA of the benign lymph nodes, with a minimum of three passes. Patients were re-evaluated with FDG-PET/CT 1 week later, with specific emphasis on the biopsied lymph nodes. RESULTS: None of the biopsied lymph nodes showed increased FDG uptake on follow-up FDG-PET/CT. No adverse events occurred. CONCLUSION: EUS-FNA prior to FDG-PET/CT did not lead to false-positive FDG uptake. The interpretive impact of minor procedures prior to FDG-PET/CT needs to be re-evaluated.

Prognostic Evaluation of 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Endometrial Cancer: A Retrospective Study.

OBJECTIVE: This study aims to ascertain if semiquantitative measurements derived from F-fluorodeoxyglucose positron emission tomography/computed tomography can be used as prognostic markers in patients with newly diagnosed endometrial cancer. MATERIALS AND METHODS: Patients with endometrial cancer and a preoperative F-fluorodeoxyglucose positron emission tomography/computed tomography before curatively intended treatment were included. The scans were evaluated using standard uptake values [maximum standard uptake value (SUVmax) and partial volume corrected (c) mean standardized uptake value (SUVmean)] and whole-body total lesion glycolysis (cTLG). All measurements were analyzed as prognostic factors in relation to overall survival (OS). Receiver operating characteristic curves were performed on all 3 positron emission tomography measurements to find the optimal cut-off for predicting OS. Multivariate Cox proportional regression models were used for prognostic evaluation. RESULTS: Eighty-three patients (median age, 69.9 y; range, 26.8-91.1) with primarily high-risk endometrial cancer or suspected high The International Federation of Gynecology and Obstetrics stage were included. Mean follow-up time was 3.48 years (range, 0.31-6.87), and 24 patients died during follow-up. In multivariate analyses with adjustment for other known prognostic factors, a SUVmax of greater than or equal to 14.3 g/mL and cSUVmean of greater than or equal to 12.7 g/mL of the primary tumor yielded a hazard ratio for OS of 3.18 (1.19-8.49) and 1.93 (0.80-4.68), respectively. Whole-body cTLG of greater than or equal to 176.1 g yielded a hazard ratio of 5.70 (1.94-16.78) for OS in a multivariate analysis. CONCLUSIONS: Preoperative SUVmax and cTLG showed potential as independent prognostic markers of OS in patients with primarily high-risk endometrial cancer. Thus, SUVmax and cTLG might help identify patients who could benefit from a more aggressive treatment strategy or closer surveillance.

Symptomatology, Clinical Presentation and Basic Work up in Patients with Suspected Pulmonary Embolism.

Basic knowledge of pulmonary embolism is relevant to most practicing physicians. Many medical specialties care for patients with increased risk of pulmonary embolism, why recognition of relevant symptoms, a thorough medical history, assessment of the clinical condition of the patient and possibly referral to a relevant facility should be a part of the skills of all clinicians. Sudden onset dyspnea, chest pain, syncope and hemoptysis are essential symptoms of pulmonary embolism, and in most of these patients basic investigations like arterial blood gas analysis, electrocardiogram, chest x-ray and biochemical analyses are appropriate. In addition, lung ultrasound and echocardiography are indicated in many of these patients. The information available from the medical history, clinical assessment and basic investigation form the basis on which the decision about further diagnostic imaging and intensity of treatment and monitoring can be made. These decisions can be guided by clinical scoring systems like the Wells score, revised Geneva score and the PESI.

Radionuclide Diagnosis of Pulmonary Embolism.

Diagnostic imaging plays an integral role in the diagnostic workup of suspected pulmonary embolism, and several modalities have been employed over the years. In recent years, the choice has been narrowed to either computer tomographic or radionuclide based methods, i.e. computer tomographic angiography (CTA) and ventilation-perfusion scintigraphy (V/Q-scan). Both methods display advantages and shortcomings, and while we provide some insights into CTA and alternative methods, the paper's main focus is a review of the V/Q-scan. We discuss basic considerations, interpretation criteria, clinical value, and controversies of conventional planar lung scintigraphy as well as the more contemporary 3-dimensional imaging technique of single photon emission tomography (SPECT) with or without CT.

Can semiquantitative measurements of SUVmax and cut-off values differentiate colorectal malignant from benign lessions?

OBJECTIVE: We investigated maximum standardized uptake value (SUVmax) and cut-off values for differentiation of malignant and benign lesions in colorectal cancer (CC) as multiple studies have questioned their validity. We also investigated more extended indices using common semi-quantification analysis in incidental colorectal findings (ICF). SUBJECTS AND METHODS: Fluorine-18-fluoro deoxy glucose positron emission tomography/computed tomography in 25 patients with a total of 30 focal ICF was retrospectively analysed using dedicated software. Method variability was tested through application of three common threshold-based lesion delineation techniques as well as a partial-volume correction (PVC). Lesion SUVmax, SUVmean, metabolically active volume (MAV) and mean total lesion glycolysis (TLG) were thereby extracted along with PVC corrected values (cSUVmean, cTLG) and SUVpeak. RESULTS: In all lesions, SUVmax was >5 and SUVmean≥2.7. Malignant SUVmax values (mean±SD: 16.5±6.2) were overall significantly higher than benign levels (9.8±3.6). There was a substantial overlap with values in polyps/adenomas (14.4±7.7). Both SUVpeak and SUVmean showed similar characteristics. Malignant MAV and TLG showed more distinct levels. Though different segmentation methods introduced variations, largest in MAV (-58.6%-141.5%), and PVC generally increased measures significantly by a factor of 1.2-2.7, neither changed relative levels much. SUVmax values were inadequate for aetiological differentiation of ICF, which also precludes a clinically significant cut-off value. The same applies to SUVpeak and SUVmean while TLG measures may be more indicative. CONCLUSION: Semi-quantitative measurements of SUVmax and cut-off values proved inadequate for differentiating colorectal malignancies from benign findings. While integrated measures, e.g. cTLG, are potentially better indicators of disease severity and extent, more optimal segmentation and PVC methods are required.

State-of-the-Art Imaging in Pulmonary Embolism: Ventilation/Perfusion Single-Photon Emission Computed Tomography versus Computed Tomography Angiography - Controversies, Results, and Recommendations from a Systematic Review.

Pulmonary embolism (PE) is a common, ubiquitous, and potentially lethal disease. As symptoms and clinical findings are notoriously nonspecific, diagnostic imaging is essential to avoid undertreatment as well as overtreatment. Controversies remain regarding first-line imaging in suspected PE. The two main contemporary contenders are ventilation/perfusion scintigraphy with single-photon emission computed tomography (V/Q SPECT) with or without additional low-dose CT (SPECT/CT) and CT angiography (CTA). We present our results from a systematic review and meta-analysis of the diagnostic performances of these modalities: V/Q SPECT, V/Q SPECT/CT, and CTA are all viable options, but we consider V/Q SPECT/CT to be superior in most clinical settings with better overall diagnostic performance, that is, pooled sensitivities (97.6 vs. 82.0%), specificities (95.9 vs. 94.9%), positive predictive values (93.0 vs. 93.8%), negative predictive values (98.6 vs. 84.7%), and accuracies (96.5 vs. 88.6%). We further address some of the ongoing controversies regarding the various modalities, that is, radiation exposure, the issues of subsegmental PE, nondiagnostic studies, and various challenges in specific patient populations.

Clinical significance of incidental focal bowel uptake on 18F-FDG PET/CT as related to colorectal cancer.

OBJECTIVE: Increased focal colorectal uptake of fluorine-18-fluorodeoxyglucose (18F-FDG) is reported to occur in 1%-3% of patients undergoing 18F-FDG positron emission tomography/computed tomography (PET/CT) for disease outside the bowel. However, there is no consensus on how to deal with this finding in the clinic. Due to the non-specific appearance of such lesions and a certain rate of false positive findings, patients may by subjected to unnecessary invasive procedures or, conversely, cancers may be overlooked if the risk of malignancy is downplayed. The purpose of this study was to examine the incidence and clinical significance of focal colorectal incidentalomas (FCI) at our institution and to assess the potential benefit of using semi-quantitative measures instead of visual interpretation to discern malignant from benign lesions. SUBJECTS AND METHODS: We identified all patients in 2011 with a report of FCI. We reviewed patient charts with regard to basic characteristics, indications for and results of 18F-FDG-PET/CT and subsequent workup including colonoscopy and histopathological analyses, and applied post hoc semi-quantitative analysis. Out of 4,829 patients, twenty-five met the inclusion criteria (mean age 71 years, 13 females, 12 males). RESULTS: Of the 25 included patients, eight presented with no pathologic or non-malignant findings (e.g. inflammation), while ten had polyps/adenomas and seven a hitherto undiagnosed colorectal cancer. Semi-quantitative SUVmax values and ROC analysis based cut-off values could not reliably discriminate benign from premalignant or malignant disease. CONCLUSION: It is the opinion of the authors that 18F-FDG PET/CT scan may identify incidentally sites of colorectal carcinoma but cannot discriminate them from polyps/adenomas. Nevertheless, incidental focal bowel uptake should always be reported and/or further evaluated.

Clinical value of FDG-PET/CT in suspected paraneoplastic syndromes: a retrospective analysis of 137 patients.

PURPOSE: Paraneoplastic syndromes (PNS) are relatively infrequent manifestations appearing before or after a cancer declares itself. Autoimmune mechanisms may be involved, but their cause and pathogenesis are often unknown. Due to disparity of symptoms, PNS remain a major diagnostic challenge. We examined the value of FDG-PET/CT for ruling in or out malignancy in a heterogeneous group of patients with suspected PNS. METHODS: We retrospectively extracted data from all patients referred 2009-2013 with suspected PNS. Data included age, sex, follow-up period, scan report, further diagnostic procedures, and final clinical diagnosis. Conclusions of the scan reports were compared to the final follow-up outcome as determined during an average follow-up of 31 months (range 6-51.5) in patients who were not diagnosed with cancer in immediate continuation of a positive PET/CT scan. RESULTS: A total of 137 patients were included. Main causes for referral were neurological (n = 67), rheumatological (n = 25), dermatological (n = 18), nephrological (n = 6), haematological (n = 2), abnormal biochemistry (n = 11), and others (n = 8). The cancer prevalence was 8.8%. The FDG-PET/CT results were as follows: nine true positives, 22 false positives, 103 true negatives, and three false negatives. Corresponding diagnostic values were: sensitivity 75%, specificity 82%, accuracy 82%, and positive and negative predictive values of 29% and 97%, respectively. CONCLUSION: FDG-PET/CT has in patients with suspected PNS an impressively high negative predictive value and may be of value in ruling out PNS, the more so, the more the number of false positives can be minimized or used in differential diagnosis. We believe that FDG-PET/CT may become an important adjunct to the work-up and triage of patients with suspected PNS.

Delayed sodium 18F-fluoride PET/CT imaging does not improve quantification of vascular calcification metabolism: results from the CAMONA study.

BACKGROUND: This study aimed to determine if delayed sodium (18)F-fluoride (Na(18)F) PET/CT imaging improves quantification of vascular calcification metabolism. Blood-pool activity can disturb the arterial Na(18)F signal. With time, blood-pool activity declines. Therefore, delayed imaging can potentially improve quantification of vascular calcification metabolism. METHODS AND RESULTS: Twenty healthy volunteers and 18 patients with chest pain were prospectively assessed by triple time-point PET/CT imaging at approximately 45, 90, and 180 minutes after Na(18)F administration. For each time point, global uptake of Na(18)F was determined in the coronary arteries and thoracic aorta by calculating the blood-pool-corrected maximum standardized uptake value (cSUV(MAX)). A target-to-background ratio (TBR) was calculated to determine the contrast resolution at 45, 90, and 180 minutes. Furthermore, we assessed whether the acquisition time-point affected the relation between cSUV(MAX) and the estimated 10-year risk for fatal cardiovascular disease (SCORE %). Coronary cSUV(MAX) (P = .533) and aortic cSUV(MAX) (P = .654) remained similar with time, whereas the coronary TBR (P < .0001) and aortic TBR (P < .0001) significantly increased with time. Even though the contrast resolution improved with time, positive correlations between SCORE % and coronary cSUV(MAX) (P < .020) and aortic cSUV(MAX) (P < .005) were observed at all investigated time points. CONCLUSIONS: Delayed Na(18)F PET/CT imaging does not improve quantification of vascular calcification metabolism. Although contrast resolution improves with time, arterial Na(18)F avidity is invariant to the time between Na(18)F administration and PET/CT acquisition. Therefore, the optimal PET/CT acquisition time-point to quantify vascular calcification metabolism is achieved as early as 45 minutes after Na(18)F administration.

Patients from general practice with non-specific cancer symptoms: a retrospective study of symptoms and imaging.

BACKGROUND: Patients with non-specific symptoms or signs of cancer (NSSC) present a challenge as they are a heterogeneous population who are not candidates for fast-track work-up in an organ-specific cancer pre-planned pathway (CPP). Denmark has a cancer pre-planned pathway for this population (NSSC-CPP), but several issues remain unclarified, for example, distribution and significance of symptoms and findings, and choice of imaging. AIM: To investigate symptoms, cancer diagnoses, and diagnostic yield of computed tomography (CT) and fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) in patients on NSSC-CPP to improve the overall diagnostic process. DESIGN & SETTING: A retrospective medical chart review in a 1-year consecutive cohort (2020). METHOD: A total of 802 referrals were reviewed for diagnostic imaging in patients with NSSP from general practices, specialist practices, or the local hospital diagnostic centre responsible for NSSC-CPP. RESULTS: The study included 248 patients; 21% had cancer, most frequently gastrointestinal cancer (27%). The most frequent symptom was weight loss (56%). CT had a sensitivity of 85%, specificity of 87%, positive predictive value (PPV) of 65%, and negative predictive value (NPV) of 96%. For 18F-FDG-PET/CT, the numbers were sensitivity 82%, specificity 62%, PPV 33%, and NPV 94%. Patients frequently underwent subsequent examinations following initial imaging. CONCLUSION: The findings were in accordance with the literature. Patients with NSSC had a cancer prevalence of 21%, most frequently gastrointestinal. The most frequent symptom was weight loss and, even as the only symptom, it is a potential marker for cancer. CT and 18F-FDG-PET/CT were sensitive with high NPV, whereas PPV was superior in CT. Better stratification by symptoms or findings is an obvious focus point for future studies to further optimise the NSSC-CPP work-up strategy.

Critical reading of scientific arcticles on diagnostic studies.

The issue of this review is diagnostic accuracy studies by means of which it can be determined how precisely a test can identify patients with or without a given target condition. Diagnostic accuracy studies vary substantially in design but usually report outcome measures such as sensitivity and specificity. Diagnostic accuracy studies can be critically appraised by using QUADAS-2. Some study characteristics to consider is the avoidance of a case-control study design, patient selection, and the reference standard. Also, the statistical imprecision and the applicability of a study to a general population are essential factors to consider.

Role of PET/CT in diagnosing and monitoring disease activity in rheumatoid arthritis: a review.

Rheumatoid Arthritis (RA) is a systemic inflammatory disorder that commonly presents with polyarthritis but can have multisystemic involvement and complications, leading to increased morbidity and mortality. The diagnosis of RA continues to be challenging due to its varied clinical presentations. In this review article, we aim to determine the potential of PET/CT to assist in the diagnosis of RA and its complications, evaluate the therapeutic response to treatment, and predict RA remission. PET/CT has increasingly been used in the last decade to diagnose, monitor treatment response, predict remissions, and diagnose subclinical complications in RA. PET imaging with [18F]-fluorodeoxyglucose ([18F]-FDG) is the most commonly applied radiotracer in RA, but other tracers are also being studied. PET/CT with [18F]-FDG, [18F]-NaF, and other tracers might lead to early identification of RA and timely evidence-based clinical management, decreasing morbidity and mortality. Although PET/CT has been evolving as a promising tool for evaluating and managing RA, more evidence is required before incorporating PET/CT in the standard clinical management of RA.

FDG-PET/CT-based respiration-gated lung segmentation and quantification of lung inflammation in COPD patients.

OBJECTIVE AND RESULTS DESCRIPTION: The study objective was to investigate the potential of quantitative measures of pulmonary inflammation by [18 F]Fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) as a surrogate marker of inflammation in COPD. Patients treated with anti-inflammatory Liraglutide were compared to placebo and correlated with inflammatory markers. 27 COPD-patients (14 receiving Liraglutide treatment and 13 receiving placebo) underwent 4D-respiratory-gated FDG-PET/CT before and after treatment. Two raters independently segmented the lungs from CT images and measured activity in whole lung, mean standard uptake values (SUVmean) corrected for lean-body-mass in the phase-matched PET images of the whole segmented lung volume, and total lesion glycolysis (TLG; SUVmean multiplied by volume). Inter-rater reliability was analyzed with Bland-Altman analysis and correlation plots. We found no differences in metabolic activity in the lungs between the two groups as a surrogate of pulmonary inflammation, and no changes in inflammation markers. The purpose of the research and brief summary of main findings. The degree of and changes in pulmonary inflammation in chronic obstructive pulmonary disease (COPD) may be difficult to ascertain. Measuring metabolic activity as a surrogate marker of inflammation by FDG-PET/CT may be useful, but data on its use in COPD including reproducibility is still limited, especially with respiration-gated technique, which should improve quantification in the lungs. We assessed several quantitative measures of metabolic activity and correlated them with inflammation markers, and we assessed reproducibility of the methods. We found no differences in metabolic activity between the two groups (before and after 40 weeks treatment with Liraglutide vs. placebo). Bland-Altman analysis showed good agreement between the two raters. TRIAL REGISTRATION: The study was conducted between February 2018 and March 2020 at the Department of Pulmonary Diseases at Hospital South West Jutland and Lillebaelt Hospital, Denmark, and registered from March 2018 at clinicaltrials.gov with trial registration number NCT03466021.

The Role of Fibroblast Activation Protein Inhibitor Positron Emission Tomography in Inflammatory and Infectious Diseases: An Updated Systematic Review.

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.

[18F]FDG PET/CT for identifying the causes of fever of unknown origin (FUO).

Fever of unknown origin (FUO) continues to be a challenging diagnosis in clinical medicine. It has more than 200 known causes, including infections, autoimmune diseases, neoplasia, and other miscellaneous disorders. Despite the development of a wide range of diagnostic tools, a specific diagnostic algorithm for FUO is not yet available. However, [18F]FDG PET/CT, which yields information on cellular metabolism, in addition to details of organ anatomy, has been shown to be successful in the FUO investigation. This study highlights the uses of [18F]FDG PET/CT in diagnosing various causes of FUO. [18F]FDG PET/CT has been increasingly used to detect septic infections, sterile inflammatory processes, and malignancies, occupying a significant portion of the known causes of FUO. It has led to a more definitive identification of the etiology of FUO and accurate clinical management. However, more in-depth studies are crucial to understanding if [18F]FDG PET/CT can be used in the work-up of FUO.