Positron emission tomography (PET) is a powerful and rapidly developing area of molecular imaging that is used to study and visualize human physiology by the detection of positron-emitting radiopharmaceuticals. Information about metabolism, receptor/enzyme function, and biochemical mechanisms in living tissue can be obtained directly from PET experiments. Unlike magnetic resonance imaging (MRI) or computerized tomography (CT), which mainly provide detailed anatomical images, PET can measure chemical changes that occur before macroscopic anatomical signs of a disease are observed. PET is emerging as a revolutionary method for measuring body function and tailoring disease treatment in living subjects. The development of synthetic strategies for the synthesis of new positron-emitting molecules is, however, not trivial. This Review highlights key aspects of the synthesis of PET radiotracers with the short-lived positron-emitting radionuclides (11)C, (18)F, (15)O, and (13)N, with emphasis on the most recent strategies.

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Summary: In six young, healthy volunteers, a novel method to determine cerebral blood flow (CBF) using magnetic reso nance (MR) bolus tracking was compared with [,sO]H20 pos itron emission tomography (PET). The method yielded para metric CBF images with tissue contrast in good agreement withRecent results indicate that it may be possible to mea sure CBF by dynamic magnetic resonance imaging (MRI) of paramagnetic contrast agent bolus passage (0stergaard et aI., 1996a). Because of the complexity of susceptibility contrast, this technique initially only al lowed determination of relative flow rates. In a prelimi nary study in six normal volunteers, the mean gray to white flow ratio was found to be in good agreement with PET literature values for age-matched subjects (0ster gaard et aI., 1996b). In a recent animal hypercapnia study (0stergaard et aI., 1998), an approach was introduced to

The receptor for advanced glycation endproducts (RAGE) is an ubiquitous, transmembrane, immunoglobulin-like receptor that exists in multiple isoforms and binds to a diverse range of endogenous extracellular ligands and intracellular effectors. Ligand binding at the extracellular domain of RAGE initiates a complex intracellular signaling cascade, resulting in the production of reactive oxygen species (ROS), immunoinflammatory effects, cellular proliferation, or apoptosis with concomitant upregulation of RAGE itself. To date, research has mainly focused on the correlation between RAGE activity and pathological conditions, such as cancer, diabetes, cardiovascular diseases, and neurodegeneration. Because RAGE plays a role in many pathological disorders, it has become an attractive target for the development of inhibitors at the extracellular and intracellular domains. This review describes the role of endogenous RAGE ligands/effectors in normo- and pathophysiological processes, summarizes the current status of exogenous small-molecule inhibitors of RAGE and concludes by identifying key strategies for future therapeutic intervention.

The field of drug-membrane interactions is one that spans a wide range of scientific disciplines, from synthetic chemistry, through biophysics to pharmacology. Cell membranes are complex dynamic systems whose structures can be affected by drug molecules and in turn can affect the pharmacological properties of the drugs being administered. In this tutorial review we aim to provide a guide for those new to the area of drug-membrane interactions and present an introduction to areas of this topic which need to be considered. We address the lipid composition and structure of the cell membrane and comment on the physical forces present in the membrane which may impact on drug interactions. We outline methods by which drugs may cross or bind to this membrane, including the well understood passive and active transport pathways. We present a range of techniques which may be used to study the interactions of drugs with membranes both in vitro and in vivo and discuss the advantages and disadvantages of these techniques and highlight new methods being developed to further this field.

Over recent years, within the community of radiopharmaceutical sciences, there has been an increased incidence of incorrect usage of established scientific terms and conventions, and even the emergence of 'self-invented' terms. In order to address these concerns, an international Working Group on 'Nomenclature in Radiopharmaceutical Chemistry and related areas' was established in 2015 to achieve clarification of terms and to generate consensus on the utilisation of a standardised nomenclature pertinent to the field. Upon open consultation, the following consensus guidelines were agreed, which aim to.

The positron-emitting radionuclide carbon-11 (11C, t1/2 = 20.3 minutes) possesses the unique potential for radiolabeling of any biological, naturally occurring, or synthetic organic molecule for in vivo positron emission tomography (PET) imaging. Carbon-11 is most often incorporated into small molecules by methylation of alcohol, thiol, amine or carboxylic acid precursors using [11C]methyl iodide or [11C]methyl triflate (generated from [11C]CO2). Consequently, small molecules that lack an easily substituted 11C-methyl group are often considered to have non-obvious strategies for radiolabeling and require a more customized approach. [11C]Carbon dioxide, [11C]carbon monoxide, [11C]cyanide, and [11C]phosgene represent alternative carbon-11 reactants to enable 11C-carbonylation. Methodologies developed for preparation of 11C-carbonyl groups have had a tremendous impact on the development of novel PET radiopharmaceuticals and provided key tools for clinical research. 11C-Carbonyl radiopharmaceuticals based on labeled carboxylic acids, amides, carbamates, and ureas now account for a substantial number of important imaging agents that have seen translation to higher species and clinical research of previously inaccessible targets, which is a testament to the creativity, utility, and practicality of the underlying radiochemistry.

When reacted in the presence of external oxidants, gold complexes are capable of catalyzing oxidative homo- and cross-coupling reactions involving the formation of new C-C bonds. Over the last few years, several cascade processes have been reported in which coupling is preceded by a gold-mediated aryl C-H functionalization or nucleophilic addition. These reactions combine the unique reactivity of gold with oxidative coupling, enabling the construction of C-C bonds between coupling partners that are not easily accessed using alternative catalysts. In this Concept paper, the development of gold-catalyzed oxidative coupling reactions is discussed focusing on C-C bond-forming reactions of broad synthetic appeal.