¹⁸F-FDG PET/CT, ⁶⁷Ga-citrate and white blood cell (WBC) scintigraphy are molecular imaging techniques currently used in the diagnostic workup of fever of unknown origin. However, it is unknown which technique fits which patient group best. A systematic literature search has been performed for original articles regarding the use of molecular imaging in fever of unknown origin. A total of 820 eligible studies were screened of which 63 articles evaluating 5094 patients met the inclusion criteria. ¹⁸F-FDG PET/CT provided good diagnostic accuracy (with a weighted mean sensitivity, specificity, positive predicting value, negative predictive value, accuracy and helpfulness of 84.4%, 61.8%, 80.7%, 67.8%, 76.3%, and 61.1%, respectively). Even within specific patient groups such as children, elderly, patients with connective tissue diseases, patients on renal replacement therapy, and HIV-infected patients, ¹⁸F-FDG PET/CT provided good diagnostic values. For ⁶⁷Ga-citrate scintigraphy, the weighted mean sensitivity, specificity, positive predictive value, negative predictive value, and helpfulness were 42.2%, 80.3%, 82.4%, 41.9%, and 42.2%, respectively. WBC scintigraphy shows a weighted mean sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 73.5%, 86.3%, 79.1%, 82.4%, and 79.5%, respectively. However, compared to ⁶⁷Ga-citrate and WBC scintigraphy, significantly more research has been performed using ¹⁸F-FDG PET/CT and ¹⁸F-FDG PET/CT has the advantage of relatively short procedural duration; it is therefore the preferred molecular diagnostic imaging technique. ⁶⁷Ga-citrate and WBC scintigraphy can only be considered if ¹⁸F-FDG PET/CT is not available.

¹⁸F-FDG-PET/CT imaging has become a key tool to evaluate infectious and inflammatory diseases. However, application of ¹⁸F-FDG-PET/CT in patients in the intensive care unit (ICU) is limited, which is remarkable since the development of critical illness is closely linked to infection and inflammation. This limited use is caused by perceived complexity and risk of planning and executing ¹⁸F-FDG-PET/CT in such patients. The aim of this systematic review was to investigate the feasibility of ¹⁸F-FDG-PET/CT in ICU patients with special emphasis on patient preparation, transport logistics and safety. Therefore, a systematic search was performed in PubMed, Embase, and Web of Science using the search terms: intensive care, critically ill, positron emission tomography and ¹⁸F-FDG or derivates. A total of 1183 articles were found of which 10 were included. Three studies evaluated the pathophysiology of acute respiratory distress syndrome, acute lung injury and acute chest syndrome. Three other studies applied ¹⁸F-FDG-PET/CT to increase understanding of pathophysiology after traumatic brain injury. The remaining four studies evaluated infection of unknown origin. These four studies showed a sensitivity and specificity between 85%-100% and 57%-88%, respectively. A remarkable low adverse event rate of 2% was found during the entire ¹⁸F-FDG-PET/CT procedure, including desaturation and hypotension. In all studies, a team consisting of an intensive care physician and nurse was present during transport to ensure continuation of necessary critical care. Full monitoring during transport was used in patients requiring mechanical ventilation or vasopressor support. None of the studies used specific patient preparation for ICU patients. However, one article described specific recommendations in their discussion. In conclusion, ¹⁸F-FDG-PET/CT has been shown to be feasible and safe in ICU patients, even when ventilated or requiring vasopressors. Specific recommendations regarding patient preparation, logistics and scanning are needed. Including ¹⁸F-FDG-PET/CT in routine workup of infection of unknown origin in ICU patients showed potential to identify source of infection and might improve outcome.

Cardiovascular diseases (CVD) are the leading cause of death worldwide and have an increasing impact on society. Precision medicine, in which optimal care is identified for an individual or a group of individuals rather than for the average population, might provide significant health benefits for this patient group and decrease CVD morbidity and mortality. Molecular imaging provides the opportunity to assess biological processes in individuals in addition to anatomical context provided by other imaging modalities and could prove to be essential in the implementation of precision medicine in CVD. New developments in single-photon emission computed tomography (SPECT) and positron emission tomography (PET) systems, combined with rapid innovations in promising and specific radiopharmaceuticals, provide an impressive improvement of diagnostic accuracy and therapy evaluation. This may result in improved health outcomes in CVD patients, thereby reducing societal impact. Furthermore, recent technical advances have led to new possibilities for accurate image quantification, dynamic imaging, and quantification of radiotracer kinetics. This potentially allows for better evaluation of disease activity over time and treatment response monitoring. However, the clinical implementation of these new methods has been slow. This review describes the recent advances in molecular imaging and the clinical value of quantitative PET and SPECT in various fields in cardiovascular molecular imaging, such as atherosclerosis, myocardial perfusion and ischemia, infiltrative cardiomyopathies, systemic vascular diseases, and infectious cardiovascular diseases. Moreover, the challenges that need to be overcome to achieve clinical translation are addressed, and future directions are provided.

Background: Standard [ ¹⁸ F]FDG PET/CT is widely used to detect infections, but is limited in differentiating bacterial infection from inflammation due to overlapping uptake patterns. This distinction is particularly challenging in fracture-related infection (FRI), due to multiple factors, including recent surgery, soft tissue injury, fracture healing, and surgical implants. Dynamic [ ¹⁸ F]FDG imaging over time may overcome this limitation by capturing a rapid, sustained uptake seen in infections, driven by ongoing immune and microbial activity, as opposed to the potentially slower uptake in inflammation. This study investigates the potential of dynamic [ ¹⁸ F]FDG PET/CT using time-activity curves (TACs) to distinguish infection from inflammation in patients with suspected FRI. Methods: A prospective study was performed in patients referred for [ ¹⁸ F]FDG PET/CT examination to detect (the extent of) FRI from December 2021 until November 2024. Final clinical diagnosis of FRI was established according to the criteria defined by the FRI consensus group and used as a reference standard. Dynamic PET imaging was performed using a long axial field-of-view PET/CT system over a 65-minute period after [ ¹⁸ F]FDG injection. TACs were analyzed to compare uptake patterns between confirmed infections and inflammation, and diagnostic accuracy was calculated and compared to conventional standard imaging. Results: Thirty-one patients with 33 fractures suspected of infection were included. Infection was clinically confirmed in 14 fractures (42%). Diagnosis of FRI based on dynamic imaging using TACs resulted in a high sensitivity of 86%, specificity of 100%, PPV of 100% and NPV of 90%, resulting in a diagnostic accuracy of 94%. In the infection group, Fracture SUV _peak increased progressively over time, while in the inflammation group, uptake appeared to reach a plateau (p < 0.001). Visual interpretation of the dynamic imaging yielded a diagnostic accuracy of 82%. For standard imaging, quantitative and visual assessments showed diagnostic accuracies of 91% and 88%, respectively. Conclusion: This proof-of-concept study demonstrates that dynamic [ ¹⁸ F]FDG PET/CT using TACs can distinguish infection from inflammation in patients with suspected FRI, with high diagnostic accuracy observed, and suggesting a potential advantage over standard imaging. Larger-scale studies are needed to validate these results and explore the full clinical potential of dynamic imaging in infection management.

Vascular graft and endograft infections (VGEI) cause a serious morbidity and mortality burden. ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) imaging is frequently used in the diagnostic workup, but the additional value of abnormal (¹⁸F-FDG active and/or enlarged) locoregional lymph nodes is unknown. In this retrospective study, the additional diagnostic value of abnormal locoregional lymph nodes on ¹⁸F-FDG PET/CT imaging for VGEI was evaluated, including 54 patients with a culture-proven VGEI (defined according to the Management of Aortic Graft Infection [MAGIC] group classification) and 25 patients without VGEI. ¹⁸F-FDG PET/CT was qualitatively and quantitatively assessed for tracer uptake and pattern at the location of the vascular graft, and locoregional lymph node uptake and enlargement (>10 mm). ¹⁸F-FDG uptake intensity and pattern independently predicted the presence of VGEI by logistic regression (Χ²: 46.19, p < 0.001), with an OR of 7.38 (95% CI [1.65, 32.92], p = 0.009) and 18.32 (95% CI [3.95, 84.88], p < 0.001), respectively. Single visual assessment of abnormal locoregional lymph nodes predicted the presence of VGEI with a sensitivity of 35%, specificity of 96%, PPV of 95%, and NPV of 41%. The visual assessment of abnormal lymph nodes after qualitative assessment of ¹⁸F-FDG uptake intensity and pattern at the vascular graft location did not independently predict the presence of VGEI by logistic regression (Χ²: 3.60, p = 0.058; OR: 8.25, 95% CI [0.74, 63.37], p = 0.096). In conclusion, detection of abnormal locoregional lymph nodes on ¹⁸F-FDG PET/CT has a high specificity (96%) and PPV (95%) for VGEI. However, it did not add to currently used ¹⁸F-FDG PET/CT interpretation criteria.