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Brain-derived neurotrophic factor (BDNF) is one of the most studied neurotrophins in the healthy and diseased brain. As a result, there is a large body of evidence that associates BDNF with neuronal maintenance, neuronal survival, plasticity, and neurotransmitter regulation. Patients with psychiatric and neurodegenerative disorders often have reduced BDNF concentrations in their blood and brain. A current hypothesis suggests that these abnormal BDNF levels might be due to the chronic inflammatory state of the brain in certain disorders, as neuroinflammation is known to affect several BDNF-related signaling pathways. Activation of glia cells can induce an increase in the levels of pro- and antiinflammatory cytokines and reactive oxygen species, which can lead to the modulation of neuronal function and neurotoxicity observed in several brain pathologies. Understanding how neuroinflammation is involved in disorders of the brain, especially in the disease onset and progression, can be crucial for the development of new strategies of treatment. Despite the increasing evidence for the involvement of BDNF and neuroinflammation in brain disorders, there is scarce evidence that addresses the interaction between the neurotrophin and neuroinflammation in psychiatric and neurodegenerative diseases. This review focuses on the effect of acute and chronic inflammation on BDNF levels in the most common psychiatric and neurodegenerative disorders and aims to shed some light on the possible biological mechanisms that may influence this effect. In addition, this review will address the effect of behavior and pharmacological interventions on BDNF levels in these disorders.

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Activated microglia are involved in the immune response of multiple sclerosis (MS). The peripheral benzodiazepine receptor (PBR) is expressed on microglia and up-regulated after neuronal injury. [11C]PK11195 is a positron emission tomography (PET) radioligand for the PBR. The objective of the present study was to investigate [11C]PK11195 imaging in MS patients and its additional value over magnetic resonance imaging (MRI) concerning the immuno-pathophysiological process. Seven healthy and 22 MS subjects were included. Semiquantitative [11C]PK11195 uptake values were assessed with normalization on cortical grey matter. Uptake in Gadolinium-lesions was significantly increased compared with normal white matter. Uptake in T2-lesions was generally decreased, suggesting a PBR down-regulation. However, uptake values increased whenever a clinical or MR-relapse was present, suggestive for a dynamic process with a transient PBR up-regulation. During disease progression, an increase of normal-appearing white matter (NAWM) uptake was found, propagating NAWM as the possible real burden of disease. In conclusion, [11C]PK11195 and PET are able to demonstrate inflammatory processes with microglial involvement in MS.

16a-18 F-fluoro-17b-estradiol ( 18 F-FES) is an estrogen receptor (ER)-specific PET tracer with various potential interesting applications. The precise contribution of this technique in current clinical practice, however, has yet to be determined. Therefore, the aim of this study was to evaluate the value of 18 F-FES PET in breast cancer patients presenting with a clinical dilemma. Methods: 18 F-FES PET examination could be requested by referring physicians for patients with a history of ER-positive breast cancer and the presence of a clinical dilemma despite complete standard work-up. All requests for 18 F-FES PET required a positive arbitration by a dedicated medical oncologist and nuclear medicine physician. The referring physician was asked to fill in validated questionnaires before, shortly after, and at more than 3 mo after 18 F-FES PET to determine indication, diagnostic value, and therapeutic consequences of 18 F-FES PET. To further validate 18 F-FES PET findings, 18 F-FES PET lesions were quantified and compared with centrally reviewed conventional imaging. Results: Thirty-three patients underwent 18 F-FES PET between December 2008 and October 2010. 18 F-FES PET was requested to evaluate equivocal lesions on conventional work-up (n 5 21), ER status in metastatic patients (n 5 10), and the origin of metastases (n 5 2). 18 F-FES-positive lesions were observed in 22 patients. 18 F-FES PET was especially sensitive for bone metastases, detecting 341 bone lesions, compared with 246 by conventional imaging. The sensitivity for liver metastases was poor, and quantification of 18 F-FES uptake in liver lesions was hampered by high physiologic background. 18 F-FES uptake was highly variable between all metastases (range of standardized uptake value, 1.20-18.81), and 45% of the patients with a positive 18 F-FES PET finding had both 18 F-FES-positive and 18 F-FES-negative metastases. 18 F-FES PET improved diagnostic understanding in 88% of the patients and led to therapy change in 48% of the patients. Conclusion: With the exception of liver metastases, whole-body imaging of ER expression with 18 F-FES PET can be a valuable additional diagnostic tool when standard work-up is inconclusive. 18 F-FES PET supported therapy decisions by improving diagnostic understanding and providing information on ER status of tumor lesions.

The purpose of this study was to compare the prognostic value of left ventricular ejection fraction (LVEF) and myocardial perfusion reserve (MPR) assessed with PET in patients with ischemic heart disease (IHD). Myocardial perfusion is the main determinant of left ventricular function in patients with IHD. The prognostic value of LVEF has been widely established. In addition, MPR determines survival in patients with hypertrophic and dilated cardiomyopathies. In the present study, we evaluated whether MPR also determines survival in patients with IHD. Methods: Between 1995 and 2003, 480 consecutive patients with chronic IHD underwent dipyridamole stress and rest 13 N-ammonia PET to determine MPR. Additionally, 18 F-FDG PET was performed for viability (mismatching defects), infarction (matching defects), and left ventricular function assessment. Patients were followed for all causes of mortality and major cardiovascular events. Results: In 463 of the 480 patients, valid MPR could be measured (368 men; mean age, 66 6 11 y; LVEF, 35% 6 15%). One hundred nineteen patients underwent a PET-driven revascularization (67 through percutaneous coronary intervention and 52 through coronary artery bypass grafting). The remaining 344 patients were the subject of this study. The overall MPR was 1.71 6 0.50 (intertertile boundaries, 1.49 and 1.84). After adjustment for age and sex, MPR was associated with a hazard ratio for cardiac death of 4.11 (95% confidence interval, 2.98-5.67) per SD decrease, whereas the risk for LVEF was 2.76 (2.00-3.82) per SD decrease. Conclusion: Patients with IHD with a low MPR are at high risk of cardiac death. MPR is a more sensitive predictor for cardiac death than is LVEF.

FDG-PET, combined with CT, is nowadays getting more and more relevant for the diagnosis of several infectious and inflammatory diseases and particularly for therapy monitoring. Thus, this paper gives special attention to the role of FDG-PET/CT in the diagnosis and therapy monitoring of infectious and inflammatory diseases. Enough evidence in the literature already exists about the usefulness of FDG-PET/CT in the diagnosis, management, and followup of patients with sarcoidosis, spondylodiscitis, and vasculitis. For other diseases, such as inflammatory bowel diseases, rheumatoid arthritis, autoimmune pancreatitis, and fungal infections, hard evidence is lacking, but studies also point out that FDG-PET/CT could be useful. It is of invaluable importance to have large prospective multicenter studies in this field to provide clear answers, not only for the status of nuclear medicine in general but also to reduce high costs of treatment.

Nuclear medicine imaging offers the possibility to study in vivo different aspects of inflammatory process by the use of radio-labeled molecules that bind to specific receptor targets on cells and tissues. This noninvasive technique, combined with pathogens engineered to express luciferase, allows quantification in the same animal of the spatial and temporal progression of the infection and identification of animal-to-animal variations in pathogen replication and dissemination. One strategy to use optical imaging in living animals is the use of luciferase reporter genes as internal sources of light called bioluminescence imaging (BLI). This enables real-time noninvasive imaging of infections and gene expression in living organisms. Nuclear medicine imaging is characterized by the use of radio pharmaceuticals (radiolabeled probes) that, administered in pico- and nanomolar amounts. These probes can also be used for early diagnosis of diseases, in susceptible subjects, for detection of disease relapse and radio-guided surgery