Current Pharmaceutical Design - Volume 24, Issue 7, 2018

In the field of inflammation imaging, nuclear medicine techniques can be considered as a non-invasive tool to early detect pathophysiological changes in affected tissues. These changes usually occur before clinical onset of symptoms and before the development of anatomical changes, that are commonly detected by radiological procedures. This is particularly important for prognostic purposes, therapy decision making and for therapy follow-up. Here we review the current state-of-the art of nuclear medicine for diagnostic purposes in different conditions characterized by a chronic inflammation, such as vulnerable atherosclerotic plaques, vasculitis, rheumatoid arthritis, Sjogren syndrome, autoimmune thyroid diseases, inflammatory bowel diseases, Coeliac disease, Type 1 diabetes mellitus and other immunological diseases. Overall, we describe several different approaches based on radiolabeled cells, peptides and antibodies or FDG. It emerges the role of PET and of hybrid cameras in particular (SPECT/CT and PET/CT) for diagnosis of these disorders and for therapy decision making and followup.

There is an increased need to find non-invasive tools for early diagnosis and follow-up of infections. Nuclear medicine techniques may be used to diagnose, localize and evaluate the severity and the extent of infections before the occurrence of anatomical abnormalities. This review focuses on different approaches based on radiolabelled cells, peptides and antibodies or [18F]FDG to image infective diseases in agreement with what is being jointly evaluated by the European Association of Nuclear Medicine (EANM). This is particularly relevant, since the EANM has strated a wide program of collaboration with other European clinical societies to define common diagnostic flow-charts in many of these infective diseases. It emerges the role of radiolabelled WBC by SPECT/CT for prosthetic joint infections and of FDG by PET/CT for spondylodiscitis. Comparable values of accuracy have been described for WBC and FDG in the diagnosis of vascular fgraft infections, diabetic gfoot, endocarditis and peripheral bone osteomyelitis, with some exceptions.

Infectious diseases remain a major health problem and cause of death worldwide. It is expected that the socio-economic impact will further intensify due to escalating resistance to antibiotics, an ageing population and an increase in the number of patients under immunosuppressive therapy and implanted medical devices. Even though radiolabeled probes and leukocytes are routinely used in clinical practice, it might still be difficult to distinguish sterile inflammation from inflammation caused by bacteria. Moreover, the majority of these probes are based on the attraction of leukocytes which may be hampered in neutropenic patients. Novel approaches that can be implemented in clinical practice and allow for swift diagnosis of infection by targeting the microorganism directly, are posing an attractive strategy. Here we review the current strategies to directly image bacteria using radionuclides and we provide an overview of the preclinical efforts to develop and validate new approaches. Indeed, significant progress has been made in the past years, but very few radiopharmaceuticals (that were promising in preclinical studies) have made it into clinical practice. We will discuss the challenges that remain to select good candidates for imaging agents targeting bacteria.

Both 67Ga and 68Ga-citrates are used to detect a wide spectrum of pathology consisting of various inflammatory, infectious and malignant conditions. Considering the now widespread availability and constantly increasing demand for PET/CT studies,68Ga-citrate is gaining ground in clinical settings and the added value of combined metabolic and anatomical imaging achieved by combining PET with Computed Tomography (CT) to PET/CT makes 68Ga-citrate particularly promising. Despite the tracer's non-specificity, it has demonstrated potential especially in the evaluation of various infectious and inflammatory skeletal- and lung conditions. In this review, we will focus on the indications and lessons learned from 67Ga, and present the current status for the use of 68Ga-citrate PET/CT in selected inflammation and infectious diseases based on the limited literature available.

Positron emission tomography (PET) is a powerful diagnostic nuclear medicine imaging technique. PET allows in vivo detection of a wide variety of physiologic and pathologic phenomena and it offers a noninvasive tool for the monitoring of therapy in various diseases. Invasive fungal infections (IFIs) are a global concern because of the increasing population of patients at risk of IFIs and the high morbidity and mortality. Therapy with antifungal agents is long-standing and expensive. The emerging resistant fungal strains make the management of IFIs challenging. There is an absolute need for a sensitive noninvasive biomarker capable of monitoring the disease activity of IFIs and determining the efficacy of treatment at an early time point. PET imaging with 18Ffluorodeoxyglucose (FDG) was used to detect and assess disease activity in IFI foci already over 20 years ago. At that time, it was suggested it could be a useful biomarker for monitoring antifungal therapy. However, this knowledge has still not been fully exploited for the management of IFIs. The literature reveals an increasing realization of the usefulness of PET in monitoring therapy of IFIs. In this review, we highlight the advantages of nuclear medicine techniques in the management of IFIs with emphasis of the role of PET in monitoring therapy efficacy.

Nuclear Medicine (NM) imaging plays a major role in the assessment of infection and inflammation. Tracers, including single photon emitting radionuclides for Single Photon Emission Tomography (SPECT) and agents for positron emission tomography (PET), reflect primarily tissue and cellular function or metabolism. In the specific clinical setting of a patient with suspected infectious or inflammatory process, planar scintigraphy, SPECT or PET procedures are used to support a clinically suspected diagnosis. Integrating metabolic and anatomic information using a single SPECT/CT or PET/CT technique has substantially improved the diagnostic accuracy of these imaging tests and advanced the NM technology to be a significant and important tool in the field of infection and inflammation. Diabetes, one of the most prevalent diseases, has a direct relationship with the development of various infection related condition. Due to alterations in different metabolic pathways, imaging of the diabetic patient may be subject to specific pitfalls and obstacles which should be taken into consideration. This review aimed at describing the impact of diabetes and hyperglycemia on NM imaging, with an emphasis on FDGPET/ CT, in specific infectious conditions related to diabetes.

Fever of Unknown Origin, or FUO, is a challenging condition for patients and clinicians. In up to 50% of cases, no diagnosis is established. Patient workup begins with comprehensive history, physical examination and laboratory tests. Radionuclide imaging has been a second-line procedure. Gallium-67 citrate, which accumulates in infection, inflammation, and tumor, was for many years, the radionuclide test of choice in the workup of FUO. The 24-72 hours between injection and imaging, relatively high radiation dose to patients, and suboptimal image quality are significant disadvantages; imaging results are variable. Although labeled leukocyte imaging accurately localizes infection, infections cause only about 20%-40% of all FUO's. In most cases, this test is not helpful in identifying the source of the fever. Fluorine-18-fluorodeoxyglucose (FDG) uptake is related to cellular glucose metabolism. Increased FDG uptake is present in numerous hypermetabolic conditions, including tumor, infection, and noninfectious inflammation. FDG positron emission tomography (PET) and PET/computed tomography (CT) have rapidly assumed an increasingly important role in the diagnostic workup of patients with FUO. FDG is especially useful for localizing lesions and areas of interest for further evaluation. In contrast to gallium and labeled leukocyte imaging, FDG contributes useful information in children with FUO. Initially utilized as a second-line diagnostic tool in patients with FUO, recent data indicate that FDG contributes more diagnostically useful information than anatomic imaging like ultrasound and CT, which leads to earlier institution of appropriate therapy. These findings suggest that FDG imaging should be performed earlier, rather than later, in the diagnostic evaluation of the patient with FUO.

The gut microbiota plays significant roles in the human body during all spheres' of life and influences innate immunity, promotes granulocyte signaling and provides resistance during pathogenic colonization of the gut; crucial for a healthy life. Antibiotics directly affect the gut microbiota that consequently alters the basic biological processes and imposes severe consequences in population falling under different age groups. In this article, we assessed the differences in microbial colonization and immune function of the intestinal tract in infants, adults, and the aged people and also examined the recent reports describing the impacts of antibiotics on infant microbiome assembly and functioning. The age old techniques have been compared to modern ones in relation to the functioning of the gut microbiome to draw inferences on significant impacts of various microbiota on human life starting from the womb, through infancy, adulthood and old age. It was observed that data is limited to different classes or origin of populace depicting variations in food habits and/or suffering from heavy metal associated diseases after continuous exposure to heavy metals/ metalloids/ biocides. Such extreme environmental factors significantly modulate the microbiota and assist in creating a 'co-resistant' gene pool that influences gut health. In the light of this finding, it is important to analyze the ‘co-resistant’ gene pool existing in gut-microbiome which supports to recoup and establish a healthy life. The hypothesis of ‘postbiotics’ is under process and their associations with antibiotic turn to be new-insight in antibiotic therapy. On one hand, postbiotics provide a great opportunity to understand the mechanism of action against pathobionts; on the other; they lead to postulation of newer pharmabiotic products and pharmacological strategies for better gut health.

Background: Chagas' disease, caused by Trypanosoma cruzi, was described for the first time over a hundred years ago. Nonetheless, clinically available drugs still lack effective and selective properties. Nitric oxide (NO) produced by activated macrophages controls the progression of disease by killing the parasite. Methods and Results: Here, chitosan nanoparticles (CS NPs) were synthesized and mercaptosuccinic acid (MSA), the NO donor precursor, was encapsulated into CS NPs, forming MSA-CS NPs, which had hydrodynamic size of 101.0±2.535 nm. Encapsulated MSA was nitrosated forming NO donor S-nitrosomercaptosuccinic acid-containing nanoparticles (S-nitroso-MSA-CS NPs). Kinetic data revealed a sustained release of NO from the nanoparticles. S-nitroso-MSA-CS NPs inhibited epimastigote proliferation and trypomastigote viability of T. cruzi, with IC50=75.0±6.5 μg·mL-1 and EC50=25.0±5.0 μg·mL-1, respectively. Treatment of peritoneal macrophages with nanoparticles decreased the number of T. cruzi-infected cells and the average number of intracellular replicative amastigotes per infected cells. Besides, the results have showed a selective behaviour of S-nitroso-MSA-CS NPs to parasites. Morphological and biochemical changes induced by these NO-releasing nanoparticles, such as cell shrinkage, cell cycle arrest, mitochondrial membrane depolarization and phosphatidylserine exposure on cell surface indicate that epimastigotes death is associated to the apoptotic pathway. Conclusion: S-nitroso-MSA-CS NPs are promising nanocarriers for the treatment of Chagas's disease.