Positron emission tomography (PET) imaging has in recent years provided not only new and exciting insights into the biochemical functions of the brain, but also radiopharmaceuticals and imaging techniques that are beginning to impact the diagnosis and treatment of neurologic and psychiatric diseases. A dominant theme of these advances has been the development, validation, and implementation of radiotracers that act as high-affinity ligands for the many important receptors, enzymes, transporters, and ion channels that comprise the functional architecture of the central nervous system. The concepts and techniques for identification of potential radioligands, methods for validation of specificity of in vivo binding in animals, and analytical tools for interpretation of human PET imaging data have now been extensively discussed.
There are, however, other conceptual approaches to brain imaging of biochemistry that do not solely depend on the high-affinity binding of a small molecule to a protein, and radiotracers of this type may better reflect functional changes in brain biochemistry. The classic example is 2-[18F]fluoro-2-deoxy-D-glucose (FDG), the most used PET radiopharmaceutical, which functions as a metabolic trapping agent following its enzymatic phosphorylation in the first step of glycolysis. The development of such in vivo radiotracers usually requires the design of novel molecules or significant modifications of known substrates or drugs, and their applications similarly often require unique models for preclinical validation and different approaches to the analyses of the in vivo pharmacokinetic data obtained from imaging studies.
These alternatives in radiotracer design, validation methods, and human imaging applications to be explored in this topic include but are not limited to the following methods and examples:
• Metabolic trapping of products from enzyme action
• Enzyme action followed by covalent attachment (suicide inhibition)
• Incorporation into macromolecules (e.g., protein and DNA synthesis)
• Membrane transport
• Acid-base equilibria
• Oxidation and reduction (e.g., redox, hypoxia, mitochondrial complex I)
• Lipophilicity (e.g., myelin imaging)
• Sequestration into vesicles and lysozomes
• Free radical trapping-free radical trapping (ROS)
We seek original research articles that involve aspects of radiotracer design, validation, and application for any of the above concepts, or any new ideas for molecular design that might be applicable to PET imaging of brain biochemistry. Review articles on these topics are also very welcome.
Positron emission tomography (PET) imaging has in recent years provided not only new and exciting insights into the biochemical functions of the brain, but also radiopharmaceuticals and imaging techniques that are beginning to impact the diagnosis and treatment of neurologic and psychiatric diseases. A dominant theme of these advances has been the development, validation, and implementation of radiotracers that act as high-affinity ligands for the many important receptors, enzymes, transporters, and ion channels that comprise the functional architecture of the central nervous system. The concepts and techniques for identification of potential radioligands, methods for validation of specificity of in vivo binding in animals, and analytical tools for interpretation of human PET imaging data have now been extensively discussed.
There are, however, other conceptual approaches to brain imaging of biochemistry that do not solely depend on the high-affinity binding of a small molecule to a protein, and radiotracers of this type may better reflect functional changes in brain biochemistry. The classic example is 2-[18F]fluoro-2-deoxy-D-glucose (FDG), the most used PET radiopharmaceutical, which functions as a metabolic trapping agent following its enzymatic phosphorylation in the first step of glycolysis. The development of such in vivo radiotracers usually requires the design of novel molecules or significant modifications of known substrates or drugs, and their applications similarly often require unique models for preclinical validation and different approaches to the analyses of the in vivo pharmacokinetic data obtained from imaging studies.
These alternatives in radiotracer design, validation methods, and human imaging applications to be explored in this topic include but are not limited to the following methods and examples:
• Metabolic trapping of products from enzyme action
• Enzyme action followed by covalent attachment (suicide inhibition)
• Incorporation into macromolecules (e.g., protein and DNA synthesis)
• Membrane transport
• Acid-base equilibria
• Oxidation and reduction (e.g., redox, hypoxia, mitochondrial complex I)
• Lipophilicity (e.g., myelin imaging)
• Sequestration into vesicles and lysozomes
• Free radical trapping-free radical trapping (ROS)
We seek original research articles that involve aspects of radiotracer design, validation, and application for any of the above concepts, or any new ideas for molecular design that might be applicable to PET imaging of brain biochemistry. Review articles on these topics are also very welcome.
