Imaging of neuroinflammation in Alzheimer's disease, multiple sclerosis and stroke: Recent developments in positron emission tomography.

Neuroinflammation is thought to play a pivotal role in many diseases affecting the brain, including Alzheimer's disease, multiple sclerosis and stroke. Neuroinflammation is characterised predominantly by microglial activation, which can be visualised using positron emission tomography (PET). Traditionally, translocator protein 18kDa (TSPO) is the target for imaging of neuroinflammation using PET. In this review, recent preclinical and clinical research using PET in Alzheimer's disease, multiple sclerosis and stroke is summarised. In addition, new molecular targets for imaging of neuroinflammation, such as monoamine oxidases, adenosine receptors and cannabinoid receptor type 2, are discussed. This article is part of a Special Issue entitled: Neuro Inflammation edited by Helga E. de Vries and Markus Schwaninger.

(11) C-labeled and (18) F-labeled PET ligands for subtype-specific imaging of histamine receptors in the brain.

The signaling molecule histamine plays a key role in the mediation of immune reactions, in gastric secretion, and in the sensory system. In addition, it has an important function as a neurotransmitter in the central nervous system, acting in pituitary hormone secretion, wakefulness, motor and cognitive functions, as well as in itch and nociception. This has raised interest in the role of the histaminergic system for the treatment and diagnosis of various pathologies such as allergy, sleeping and eating disorders, neurodegeneration, neuroinflammation, mood disorders, and pruritus. In the past 20 years, several ligands targeting the four different histamine receptor subtypes have been explored as potential radiotracers for positron emission tomography (PET). This contribution provides an overview of the developments of subtype-selective carbon-11-labeled and fluorine-18-labeled compounds for imaging in the brain. Using specific radioligands, the H1 R expression in human brain could be examined in diseases such as schizophrenia, depression, and anorexia nervosa. In addition, the sedative effects of antihistamines could be investigated in terms of H1 R occupancy. The H3 R is of special interest because of its regulatory role in the release of various other neurotransmitters, and initial H3 R PET imaging studies in humans have been reported. The H4 R is the youngest member of the histamine receptor family and is involved in neuroinflammation and various sensory pathways. To date, two H4 R-specific (11) C-labeled ligands have been synthesized, and the imaging of the H4 R in vivo is in the early stage.

3'-Sulfonylesters of 2,5'-anhydro-1-(2-deoxy-beta-d-threo-pentofuranosyl)thymine as precursors for the synthesis of [(18)F]FLT: syntheses and radiofluorination trials.

Title compounds [3'-sulfonylesters of 2,5'-anhydro-1-(2-deoxy-beta-d-threo-pentofuranosyl)thymine: 2,5'-anhydro-1-(2-deoxy-3-methanesulfonyl-beta-d-threo-pentofuranosyl)thymine (1a); 2,5'-anhydro-1-(2-deoxy-3-(4-nitrobenzenesulfonyl)-beta-d-threo-pentofuranosyl)thymine (1b); 2,5'-anhydro-1(-2-deoxy-3-(toluenesulfonyl)-beta-d-threo-pentofuranosyl)thymine (1c); and 2,5'-anhydro-1(-2-deoxy-3-(2,2,2-trifluoroethanesulfonyl)-beta-d-threo-pentofuranosyl)thymine 1d] were synthesized, and their use as starting materials for the synthesis of 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT) was investigated. Radiofluorination of Compound 1b and subsequent hydrolysis with NaOH, in solution or on solid support, yielded a product with the same retention on radio thin-layer chromatography as [(18)F]FLT. However, careful analysis with high-performance liquid chromatography could not identify the product to be [(18)F]FLT. From several options that were investigated to identify the obtained product, it was shown that fluorination had occurred at the nitro group of the nosylate, and not at the 3'-position. Other sulfonate esters (Compounds 1a, 1c and 1d) did not give any fluorination under any of the investigated reaction conditions. It had to be concluded that title compounds are not suitable as starting materials for the synthesis of [(18)F]FLT under the described conditions.