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Over the last decades, the population at risk for invasive fungal disease (IFD) has increased because of medical therapy advances and diseases compromising patients' immune systems. The high morbidity and mortality associated with invasive fungal disease in the immunocompromised present the challenge of early diagnosis of the IFD and the need to closely monitor the infection during treatment. The definitive diagnosis of invasive fungal disease based on culture or histopathological methods often has reduced diagnostic accuracy in the immunocompromised and may be very invasive. Less invasive and indirect evidence of the fungal infection by serology and imaging has been used for the early diagnosis of fungal infection before definitive results are available or when the definitive methods of diagnosis are suboptimal. Imaging in invasive fungal disease is a non-invasive biomarker that helps in the early diagnosis of invasive fungal disease but helps follow-up the infection during treatment. Different imaging modalities are used in the workup to evaluate fungal disease. The different imaging modalities have advantages and disadvantages at different sites in the body and may complement each other in the management of IFD. Positron emission tomography integrated with computed tomography with [18F]Fluorodeoxyglucose (FDG PET/CT) has helped manage IFD. The combined functional data from PET and anatomical data from the CT from almost the whole body allows noninvasive evaluation of IFD and provides a semiquantitative means of assessing therapy. FDG PET/CT adds value to anatomic-based only imaging modalities. The nonspecificity of FDG uptake has led to the evaluation of other tracers in the assessment of IFD. However, these are mainly still at the preclinical level and are yet to be translated to humans. FDG PET/CT remains the most widely evaluated radionuclide-based imaging modality in IFD management. The limitations of FDG PET/CT must be well understood, and more extensive prospective studies in uniform populations are needed to validate its role in the management of IFD that can be international guidelines.

A. PET uptake in the circulation per cohort, as determined by region of interest drawn in left ventricle; cohort 1 (in blue) contained 2 patients (0 mg additional MMOT0530A), cohort 2 (in green) contained 9 patients (10 mg additional MMOT0530A). On X axis the different PET moments: 2, 4 and 7 days post injection. On the Y axis the mean SUVmax per cohort.

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Purpose: Mesothelin (MSLN) is frequently overexpressed in pancreatic and ovarian cancers, making it a potential drug target. We performed an 89Zr-PET imaging study with MMOT0530A, a MSLN antibody, in conjunction with a phase I study with the antibody–drug conjugate DMOT4039A, containing MMOT0530A bound to MMAE. The aim was to study antibody tumor uptake, whole-body distribution, and relation between uptake, response to treatment, and MSLN expression.Experimental Design: Before DMOT4039A treatment, patients received 37 MBq 89Zr-MMOT0530A followed by PET/CT imaging 2, 4, and 7 days postinjection. Tracer uptake was expressed as standardized uptake value (SUV). MSLN expression was determined with immunohistochemistry (IHC) on archival tumor tissue.Results: Eleven patients were included, 7 with pancreatic and 4 with ovarian cancer. IHC MSLN expression varied from absent to strong. Suitable tracer antibody dose was 10 mg MMOT0530A and optimal imaging time was 4 and 7 days postinjection. Tumor tracer uptake occurred in 37 lesions with mean SUVmax of 13.1 (±7.5) on PET 4 days postinjection, with 11.5 (±7.5) in (N = 17) pancreatic and 14.5 (±8.7) in (N = 20) ovarian cancer lesions. Within patients, a mean 2.4-fold (±1.10) difference in uptake between tumor lesions existed. Uptake in blood, liver, kidneys, spleen, and intestine reflected normal antibody distribution. Tracer tumor uptake was correlated to IHC. Best response to DMOT4039A was partial response in one patient.Conclusions: With 89Zr-MMOT0530A-PET, pancreatic and ovarian cancer lesions as well as antibody biodistribution could be visualized. This technique can potentially guide individualized antibody-based treatment. Clin Cancer Res; 22(7); 1642–52. ©2015 AACR.

Purpose: PET with 16α-[18F]-fluoro-17β-estradiol ([18F]FES) allows assessment of whole body estrogen receptor (ER) expression. The aim of this study was to investigate [18F]-fluorodeoxyglucose ([18F]FDG) and [18F]FES PET/CT imaging for response prediction and monitoring of drug activity in patients with metastatic ER-positive breast cancer undergoing treatment with the selective estrogen receptor downregulator (SERD) rintodestrant. Experimental Design: In this trial (NCT03455270), PET/CT imaging was performed at baseline ([18F]FDG and [18F]FES), during treatment and at time of progression (only [18F]FES). Visual, quantitative, and mutational analysis was performed to derive a heterogeneity score (HS) and assess tracer uptake in lesions, in relation to the mutation profile. The primary outcome was progression-free survival (PFS). Results: The HS and PFS in the entire group did not correlate (n = 16, Spearman's rho, P = 0.06), but patients with a low HS (< 25.0%, n = 4) had a PFS of > 5 months whereas patients with no [18F]FES uptake (HS 100.0%, n = 3) had a PFS of < 2 months. [18F]FES uptake was not affected by estrogen receptor 1 (ESR1) mutations. On-treatment [18F]FES PET/CT scans showed no [18F]FES uptake in any of the baseline [18F]FES-positive lesions. At progression, [18F]FES uptake remained blocked in patients scanned ≤ 1–2 half-lives of rintodestrant whereas it restored in patients scanned ≥ 5 days after end of treatment. Conclusions: Absence of ER expression on [18F]FES PET is a predictor for no response to rintodestrant. [18F]FES uptake during treatment and at time of progression is useful to monitor the (reversible) effect of therapy and continued mode of action of SERDs. See related commentary by Linden and Mankoff, p. 2015

Musculoskeletal infections are highly feared, form a major burden on healthcare, and may lead to severe morbidity and mortality. The diagnosis may be difficult with non-specific symptoms requiring multiple diagnostic investigations. FDG-PET/CT is one of them showing good diagnostic accuracy in most musculoskeletal infections. However, one has to be aware of the non-specific FDG uptake in patients with metallic implants and in the postsurgical phase. In this chapter, the advantages and disadvantages of the use of FDG-PET/CT in musculoskeletal infections in described for several indications: infections in the peripheral bone, spine infections/spondylodiscitis, prosthetic joint infections, diabetic foot infections, and sternal bone/wound infections. Recent published guidelines and diagnostic flowcharts by delegates of the European Association of Nuclear Medicine in collaboration with delegates from other (clinical) societies, will be discussed. At the end of this chapter, recent developments in tracer and camera systems will be presented.

Background: Poor oral health has long been associated with the development of systemic disease. The risk of infective endocarditis (IE) after dental procedures is a typical example. However, the literature is conflicting about the causal relationship between oral bacterial pathogens and risk of IE. [18F]FDG PET/CT has proven to be a useful diagnostic tool in patients with suspected IE. This study focused on: 1) the correlation between increased glucose metabolism on [18F]FDG PET/CT scans, recent dental treatment, and inflammation and/or infection sites in the oral cavity reported by the dentist; and 2) a possible correlation between IE and oral health status based on (extra)cardiac findings on [18F]FDG PET/CT scans. Methods: This retrospective study included 52 patients (32 men, 20 women; median age, 58 years; IQR [44-66] years). A total of 19 patients were diagnosed with IE (group 1), 14 patients with possible IE (group 2), and 19 patients were not diagnosed with IE based on the modified Duke criteria (group 3). Patient characteristics and dental records were reviewed for relevant clinical data at the time the [18F]FDG PET/CT scan was performed. All [18F]FDG PET/CT scans were examined visually by pattern recognition using a three-point scale, and semi-quantified within the volume of interest (VOI) using SUVmax. The Fisher’s exact probability test and Pearson’s correlation were used to analyze the relationship between dental oral cavity findings and [18F]FDG PET/CT scans. A one-way ANOVA was conducted to compare the SUVmax measured in the oral cavity. To analyze the differences among visual [18F]FDG uptake scores in groups 1, 2, and 3, the Kruskal-Wallis H test was used. Results: No correlation was found between visual [18F]FDG uptake scores and SUVmax as a marker of [18F]FDG uptake and possible sites of oral inflammation and infection, or dental treatments based on the dental records of 52 patients. Between groups 1, 2, and 3, the visual [18F]FDG uptake scores (H(2) = 4.359, p = .113) and SUVmax (F(2, 69) = 0.27, p = .798) were not significantly different. A significant difference in SUVmax of the valve for the three groups (F(2, 309) = 28.06, p < .001) was observed.Conclusions: The results of this retrospective study suggest that no correlation exists between [18F]FDG PET/CT uptake in the oral cavity and dental treatments or inflammation/infection reported by the dentist. Furthermore, no correlation between IE and actual oral health status was demonstrated. This study revealed no causal relationship between oral pathogens and risk of IE. Additional research is needed to conclude whether [18F]FDG PET/CT imaging is a reliable diagnostic modality for oral inflammation and infection sites.

The authors regret there were mistakes in Table 12 concerning adjusted risk estimation for surgical site infections of the lower limbs. The authors would like to thank Dr Tresson and colleagues for their careful reading and to apologise for any inconvenience. Table 12 should be read as below

Tuberculosis (TB) is currently the world's leading cause of infectious mortality. Imaging plays an important role in the management of this disease. The complex immune response of the human body to Mycobacterium tuberculosis results in a wide array of clinical manifestations, making clinical and radiological diagnosis challenging. F-18-FDG-PET/CT is very sensitive in the early detection of TB in most parts of the body; however, the lack of specificity is a major limitation. F-18-FDG-PET/CT images the whole body and provides a pre-therapeutic metabolic map of the infection, enabling clinicians to accurately assess the burden of disease. It enables the most appropriate site of biopsy to be selected, stages the infection, and detects disease in previously unknown sites.F-18-FDG-PET/CT has recently been shown to be able to identify a subset of patients with latent TB infection who have subclinical disease. Lung inflammation as detected by F-18-FDG-PET/CT has shown promising signs that it may be a useful predictor of progression from latent to active infection. A number of studies have identified imaging features that might improve the specificity of F-18-FDG-PET/CT at some sites of extrapulmonary TB. Other PET tracers have also been investigated for their use in TB, with some promising results. The potential role and future perspectives of PET/CT in imaging TB is considered. Literature abounds on the very important role of F-18-FDG-PET/CT in assessing therapy response in TB. The use of F-18-FDG for monitoring response to treatment is addressed in a separate review. (C) 2017 Elsevier Inc. All rights reserved.

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