Introduction

The diagnosis of an infection by means of imaging modalities mainly relies on the possibility to exclude aseptic inflammation due to degenerative process, or autoimmune/allergic reactions or simply irritative causes. Several radiological and Nuclear Medicine procedures are, therefore, involved, in the search of which modality is more accurate in which clinical setting.

From the Nuclear Medicine point-of-view, this challenge to differentiate an infection from a sterile inflammation, has led to the production of hundreds of different radiopharmaceuticals that have open new ways to the possibility to specifically image the underlying process from a molecular point of view [1, 2].

Radiolabelled antibiotics [3, 4] or glucose derived sugars [5,6,7,8] have shown the potential to image bacteria, and, on the other hand, radiolabelled cytokines [9] or monoclonal antibodies [10] open the possibility to image different white blood cell subsets for histopathological characterization in vivo of the inflammatory/infective process.

Despite this enthusiastic output of new radiopharmaceuticals, the scintigraphy with radiolabelled white blood cells (WBCs), developed in early 1970 [11, 12], remains the Nuclear Medicine modality of choice for routine and accurate diagnosis of infection. Over the years, we learned that this technique strictly relies on the application of precise labelling modalities, image acquisition protocol and interpretation criteria that have been published as guidelines by the European Association of Nuclear Medicine (EANM) [13,14,15,16,17,18].

In the last two decades, given the increasing availability and application of positron emission tomography/computed tomography (PET/CT) with 18Fluorine-fluorodeoxyglucose ([18F]FDG) in several clinical contexts, infection and inflammation have also been extensively studied [19].

The great sensitivity of [18F]FDG, together with the high quality of images provided by new generation tomographs, suggest the use of this modality for both diagnostic and follow-up purposes [19].

Nevertheless, well-standardized interpretation criteria, as it has been done for radiolabelled WBC scintigraphy, still do not exist for many infective or inflammatory disorders, thus resulting in different approaches adopted by each centre, and, most important, in a wide variability of reported accuracies of this modality that do not allow to make a direct comparison of different studies.

The need of well standardized protocols for acquisition and interpretation of [18F]FDG PET/CT images in this field, has become essential amongst the Nuclear Medicine community, as demonstrated by the increasing number of consensus documents and proposed interpretation criteria that have been published, for example, for imaging of prosthetic joint infections [20,21,22,23,24], diabetic foot osteomyelitis [25,26,27], cardiovascular inflammations and infections [18, 28,29,30,31,32,33,34], spondylodiscitis [35], inflammatory bowel diseases [36] and, more recently, for imaging with [18F]FDG by PET/Magnetic Resonance Imaging (MRI) [37, 38].

Nonetheless, the proposed interpretation criteria for [18F]FDG PET/CT imaging in many clinical indications still need to be universally validated.

Purpose

This mini-review aims at providing an overview on the state of art of [18F]FDG PET/CT imaging in musculoskeletal infections, cardiovascular infections and inflammations, and systemic inflammatory and infective diseases with particular emphasis on image acquisition protocols and interpretation criteria.

Methods

In this mini-review, we summarize the available procedural recommendations for [18F]FDG PET/CT imaging in several infective and inflammatory conditions as derived from the literature of the past 20 years. An accurate and detailed analysis of the role of [18F]FDG PET/CT in each specific indication, resulting from an expert consensus, will be provided in the following article of this Special Issue of Clinical and Translational Imaging. In particular, an extensive literature research has been carried on the role of [18F]FDG PET/CT in osteomyelitis, prosthetic joint infections, spondylodiscitis, diabetic foot infections, infective endocarditis (both native an prosthetic valve endocarditis), cardiac implantable electronic devices infection, left ventricular assist device-associated infections, vascular graft infections, large vessel vasculitis, cardiac sarcoidosis, fever and inflammation of unknown origin, systemic sarcoidosis, inflammatory bowel disease, retroperitoneal fibrosis, fungal infections, tuberculosis and SARS CoV-2 infection.

In particular, each topic was summarized according to the following scheme:

  • Clinical indications: gives an overview of the specific indications for the execution of [18F]FDG PET/CT in the diagnostic setting, for therapy evaluation or follow-up.

  • Patient preparation: describes specific protocols, when required, that need to be adopted to increase the accuracy of this modality in detecting a specific disease.

  • Imaging protocol: explains those specific acquisition protocols used for inflammatory and infective disease, when available.

  • Interpretation criteria: provides a panoramic overview of recently published interpretation criteria of [18F]FDG PET/CT imaging in each specific disease.

  • Possible pitfalls: this section summarizes the most frequently observed pitfalls and artefacts that need to be considered for a correct interpretation of the scan.

  • Final report: describes how to report the exam (in addition to demographic data and technical information of the scan, type of tomograph, body weight and administered dose) with a focus on essential parts of the report. Time between injection and image acquisition should always be included in the report since it could be particularly useful for both long-term follow-up and therapy evaluation studies when SUVmax are compared.

Results

Results are summarized in easy to read tables, aiming at proving a useful tool in daily practice (Tables 1, 2, 3, and 4).

Table 1 Summary table on [18F]FDG PET/CT imaging in cardiovascular infections/inflammations
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Table 2 Summary table on [18F]FDG PET/CT imaging in musculoskeletal infections/inflammations
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Table 3 Summary table on [18F]FDG PET/CT imaging in systemic inflammations
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Table 4 Summary table on [18F]FDG PET/CT imaging in fungal and viral infections
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It emerges that standardized protocols for patient preparation, image acquisition and interpretation criteria exist only for very limited clinical indications in the field of infection and inflammation and, in particular, for infective endocarditis, cardiac implantable devices infections, left ventricular assist device-associated infections, cardiac sarcoidosis, large vessel vasculitis and spondylodiscitis. For all other clinical indications, the recommendations for patient preparation and the acquisition protocols, commonly adopted for oncologic studies, are currently applied. As far as image interpretation is concerned, several criteria have been proposed for vascular graft infections, osteomyelitis, diabetic foot infections, prosthetic joint infections, and systemic infections/inflammations, but they still need to be validated in larger multicentre studies being the reported diagnostic accuracy of single centre studies, extremely variable and generally lower than the diagnostic accuracy of WBC scintigraphy [20, 27].

Conclusions

In summary, this article and the following, published in this journal, provide a useful tool for identifying several patterns of [18F]FDG uptake able to discriminate between an infection and a sterile inflammation aiming at increasing the specificity and the accuracy of this radiopharmaceutical. This may have a great clinical impact on the management of each specific disease, may help to smooth the wide heterogeneity that is still evident in literature and will lay the basis for future comparative studies.

The definition of disease-specific acquisition protocols is warranted to increase the specificity and accuracy of this imaging modality. Moreover, it is mandatory, that the definition of precise and standardized interpretation criteria for [18F]FDG PET/CT imaging in different infective or inflammatory disorders need to be adopted and shared by several institutions and validated in large, possibly multicentre, studies.

Teaching points

  • [18F]FDG has been proposed for the study of several inflammatory and infective diseases.

  • Standardized acquisition and interpretation protocols exist for infective endocarditis and cardiac implantable electronic devices infections, cardiac sarcoidosis, large vessel vasculitis, as well as spondylodiscitis.

  • Multicentre studies are needed to standardize the use of [18F]FDG in other inflammatory/infective diseases.

  • Tables presented in this article can be used as a base for future studies.