Radiotracers for Imaging of Inflammatory Biomarkers TSPO and COX-2 in the Brain and in the Periphery.

Inflammation involves the activation of innate immune cells and is believed to play an important role in the development and progression of both infectious and non-infectious diseases such as neurodegeneration, autoimmune diseases, pulmonary and cancer. Inflammation in the brain is marked by the upregulation of translocator protein (TSPO) in microglia. High TSPO levels are also found, for example, in macrophages in cases of rheumatoid arthritis and in malignant tumor cells compared to their relatively low physiological expression. The same applies for cyclooxgenase-2 (COX-2), which is constitutively expressed in the kidney, brain, thymus and gastrointestinal tract, but induced in microglia, macrophages and synoviocytes during inflammation. This puts TSPO and COX-2 in the spotlight as important targets for the diagnosis of inflammation. Imaging modalities, such as positron emission tomography and single-photon emission tomography, can be used to localize inflammatory processes and to track their progression over time. They could also enable the monitoring of the efficacy of therapy and predict its outcome. This review focuses on the current development of PET and SPECT tracers, not only for the detection of neuroinflammation, but also for emerging diagnostic measures in infectious and other non-infectious diseases such as rheumatic arthritis, cancer, cardiac inflammation and in lung diseases.

PET Radiopharmaceuticals for Alzheimer's Disease and Parkinson's Disease Diagnosis, the Current and Future Landscape.

Ironically, population aging which is considered a public health success has been accompanied by a myriad of new health challenges, which include neurodegenerative disorders (NDDs), the incidence of which increases proportionally to age. Among them, Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common, with the misfolding and the aggregation of proteins being common and causal in the pathogenesis of both diseases. AD is characterized by the presence of hyperphosphorylated τ protein (tau), which is the main component of neurofibrillary tangles (NFTs), and senile plaques the main component of which is ß-amyloid peptide aggregates (Aß). The neuropathological hallmark of PD is α-synuclein aggregates (α-syn), which are present as insoluble fibrils, the primary structural component of Lewy body (LB) and neurites (LN). An increasing number of non-invasive PET examinations have been used for AD, to monitor the pathological progress (hallmarks) of disease. Notwithstanding, still the need for the development of novel detection tools for other proteinopathies still remains. This review, although not exhaustively, looks at the timeline of the development of existing tracers used in the imaging of Aß and important moments that led to the development of these tracers.

Attenuation of neurological deficit by a novel ethanolamine derivative in rats after brain trauma.

Objectives: To prove that our novel ethanolamine derivative (FDES) can normalize overall movement and exploratory activity of rats with traumatic brain injury (TBI) owing to its peculiar properties. Materials and methods: TBI was modeled using controlled cortical impact injury (CCI) model method. The resulting neurological deficit, efficacy of the novel agent and other reference agents used were assayed in tests which evaluated overall movements and exploratory behavior of the rats. Finally, scopolamine in equimolar dose was used to estimate the role of cholinergic system in the efficacy of our agent. The tests included: limb-placing, open field, elevated plus maze, cylinder, and beam walking tests. Results: Intraperitoneal administration of FDES at a dose of 10 mg/kg led to improvement of fore- and hind-limb functions of rats with traumatic brain injury as was shown in "Limb placing", "Open field" "Cylinder" and "Beam walking" tests. The new agent had no effects on traumatized rats behavior in the "Elevated Plus Maze" test. Simultaneous co-administration of scopolamine with FDES reduced the beneficial effects of the latter in rats with trauma. Conclusion: The neuroprotective effects of new agent were manifested in the reduction of motor deficiencies, and exploratory activity in the CCI model rats. In comparison with choline alfoscerate and citicoline, FDES showed more beneficial effects as were observed in most of the tests, and did not negatively influence the traumatized rats psychologically. Notably, it is possible that the neuroprotective influence of the new agent is mediated by its actions on the cholinergic system.