December 2015
The value of 18F-FDG PET/CT in fever of unknown origin I.J.E. Kouijzer, MD The value of 18F-FDG PET/CT in metastatic infectious disease F.J. Vos, MD, PhD 18F-FDG PET/CT in cardiac implant infection and endocarditis A.M. Scholtens, MD De waarde van PET voor inflammatoire reumatische ziektebeelden C.J. van der Laken, MD, PhD Hybrid PET/MR imaging in the diagnosis of cardiovascular diseases: feasibility and initial results S. Vöö MD,PhD In vivo imaging of inflammation; what’s next? E.H.J.G. Aarntzen, PhD A fungus-like bacterium: Actinomyces E.H.J.G. Aarntzen, PhD CURSUS- EN CONGRESAGENDA Editorial Hybrid PET/(CT/MR) in infectious and inflammatory diseases Despite its relative short history, nuclear medicine is playing an important role in the diagnosis of infectious and inflammatory diseases. In this regard, already in the 1970s, planar imaging with labelled white blood cell scintigraphy was proven successful. Non-specific radiolabelled compounds, such as 67Ga-citrate, polyclonal human immunoglobulin (HIG), or more specific like anti-E-selectin, anti-granulocyte antibodies, cytokines, ciprofloxacin or antimicrobial peptides were either less successful or are still under research. Furthermore, the introduction of new techniques like SPECT led to higher sensitivity to detect infectious and inflammatory diseases, and hybrid camera techniques such as SPECT/CT helped to improve both the specificity and the diagnostic accuracy, due to the synergy of the anatomical and pathophysiological information it provides. Since 2002, hybrid clinical PET/CT systems (PET + multislice CT) are available. The combination of high sensitivity PET images fused with high resolution CT images has gained an almost immediate widespread clinical acceptance for diagnosis, staging and re-staging as well as prediction of response to treatments in oncology. In the USA the costs of PET/(CT) scans are reimbursed by the Centers for Medicare and Medicaid Services (CMS). In the opinion of the CMS National Coverage Determination there are clear indications for 18F-FDG PET/CT, besides oncology, in diseases of the heart and the brain (i.e. myocardial perfusion, seizures and the differential diagnosis of frontotemporal dementia and Alzheimer’s disease). Apparently, the non-specificity of FDG is very well recognised, but so far the use of FDG PET/CT in infectious and inflammatory diseases is not reimbursed. This lack of reimbursement in the USA is most likely the reason that a large proportion of publications that report on the use of 18F-FDG PET/CT in diagnosing infectious and inflammatory diseases, originate from Europe. Because infectious and inflammatory conditions form a very heterogeneous group of diseases, and patients may present with a variety of symptoms, diagnosis can be an important problem to the clinician. Usually, after initial laboratory tests, various conventional imaging procedures are consulted (X-ray, ultrasound, CT and/or MRI) to reveal anatomical changes. However, in the early stages of disease, morphologic changes or abnormalities may be absent, so anatomic imaging modalities have a rather low sensitivity for early stage disease. In addition, these techniques usually provide information on a limited part of the body, and e.g. the use of total body MRI is not widespread. Moreover, when morphologic changes are found after surgery or other therapeutic interventions, differentiation of infection/inflammation from residual changes is limited. Performing 18F-FDG PET/CT in an early stage of disease may be beneficial for an early diagnosis. However, it remains a challenge to define when the benefits of a hybrid PET/CT outweigh the costs. In this special issue of the TvNG readers will learn more about the work of Dutch colleagues on infectious and inflammatory issues. The first contribution is by Kouijzer et al from Radboud University Medical Center (UMC) Nijmegen. They claim 18F-FDG PET/CT is cost-effective in patients with ‘fever of unknown origin’ (FUO) because an adequate and early diagnosis in FUO limits the number of non-contributing, often invasive, tests and the duration of hospitalisation. Note: a first attempt to describe the costeffectiveness of 18F-FDG PET/CT in ‘inflammation of unknown origin’ was published in a previous issue of this journal (TvNG. 2015,37(2):1409-11). Vos et al, also attached to Radboud UMC Nijmegen, describe the value of 18F-FDG PET/CT in metastatic infectious disease and suggest it should be performed in all patients with high risk Gram-positive bacteraemia. Scholtens from Meander Medical Center at Amersfoort reports on the value of 18F-FDG PET/CT in cardiovascular infection and endocarditis. Van der Laken, from VUMC Amsterdam, discusses the use of 18F-FDG and 18F-fluoride PET/CT next to MRI in the field of rheumatology, bearing in mind that the efficacy of expensive biologicals (E€20.000/patient/year) is only 50-70%. Also clinical results with 11C-PK11195 PET as a marker of activated) macrophages are discussed. Note: of particular interest for daily clinical practice is a recent overview by Glaudemans et al from UMC Groningen on pitfalls and limitations of hybrid imaging in infection and inflammation (Sem Nucl Med. 2015,45:500-12). Hybrid PET/MRI is a different ball game: it presents soft tissue contrast better and causes less radiation exposure in simultaneous imaging settings, theoretically resulting in improved matching of the images. Voo et al from Maastricht UMC also recognise a certain downside, MRI protocols increase workflow complexity and are, compared with CT, time-consuming and requiring more patient compliance. However, based on their positive first clinical experiences, it is likely that hybrid PET/MRI will become a valuable imaging approach in the diagnosis of many cardiovascular diseases, including inflammatory pathologies such as myocarditis, cardiac sarcoidosis, or large vessel vasculitis. New developments in radiochemistry and e.g. peptide chemistry will hopefully result in more selective tracers with high specific activity. As inflammation is a nonspecific process (e.g. occurring both in malignancy and infection), a tracer that may differentiate between inflammation and infection is regarded to be the ‘Holy Grail’. However, so far such a tracer has not been established. Aarntzen and Boerman, affiliated with Radboud UMC Nijmegen, discuss the main categories of clinical available techniques for in vivo immune cell imaging. They highlight the current developments envisioned to have clinical impact in the upcoming years. Hopefully, this special issue contributes to the increasing insight that hybrid nuclear medicine offers powerful non-invasive techniques for visualisation of infectious and inflammatory disorders. Especially the use of whole body imaging that enables the determination of both localisation and the number of infectious/inflammatory foci. Results of hybrid nuclear medicine investigations may therefore play a crucial role in ‘specialised’ or ‘personalised’ medicine. Hans Balink, MD, PhD Guest editor
€ 5,95