The dynamic and multicellular processes of neuroinflammation are mediated by the nonneuronal cells of the central nervous system, which include astrocytes and the brain’s resident macrophages, microglia. Although initiation of an inflammatory response may be beneficial in response to injury of the nervous system, chronic or maladaptive neuroinflammation can have harmful outcomes in many neurological diseases. An acute neuroinflammatory response is protective when activated neuroglia facilitate tissue repair by releasing anti-inflammatory cytokines and neurotrophic factors. On the other hand, chronic neuroglial activation is a major pathological mechanism in neurodegenerative diseases, likely contributing to neuronal dysfunction, injury, and disease progression. Therefore, the development of specific and sensitive probes for positron emission tomography (PET) studies of neuroinflammation is attracting immense scientific and clinical interest. An early phase of this research emphasized PET studies of the prototypical imaging biomarker of glial activation, translocator protein-18 kDa (TSPO), which presents difficulties for quantitation and lacks absolute cellular specificity. Many alternate molecular targets present themselves for PET imaging of neuroinflammation in vivo, including enzymes, intracellular signaling molecules as well as ionotropic, G-protein coupled, and immunoglobulin receptors. We now review the lead structures in radiotracer development for PET studies of neuroinflammation targets for neurodegenerative diseases extending beyond TSPO, including glycogen synthase kinase 3, monoamine oxidase-B, reactive oxygen species, imidazoline-2 binding sites, cyclooxygenase, the phospholipase A2/arachidonic acid pathway, sphingosine-1-phosphate receptor-1, cannabinoid-2 receptor, the chemokine receptor CX3CR1, purinergic receptors: P2X7 and P2Y12, the receptor for advanced glycation end products, Mer tyrosine kinase, and triggering receptor expressed on myeloid cells-1. We provide a brief overview of the cellular expression and function of these targets, noting their selectivity for astrocytes and/or microglia, and highlight the classes of PET radiotracers that have been investigated in early-stage preclinical or clinical research studies of neuroinflammation.
PurposeThis short review aims to cover the more recent and promising developments of carbon-11 (11C) labeling radiochemistry and its utility in the production of novel radiopharmaceuticals, with special emphasis on methods that have the greatest potential to be translated for clinical positron emission tomography (PET) imaging.MethodsA survey of the literature was undertaken to identify articles focusing on methodological development in 11C chemistry and their use within novel radiopharmaceutical preparation. However, since 11C-labeling chemistry is such a narrow field of research, no systematic literature search was therefore feasible. The survey was further restricted to a specific timeframe (2000–2016) and articles in English.ResultsFrom the literature, it is clear that the majority of 11C-labeled radiopharmaceuticals prepared for clinical PET studies have been radiolabeled using the standard heteroatom methylation reaction. However, a number of methodologies have been developed in recent years, both from a technical and chemical point of view. Amongst these, two protocols may have the greatest potential to be widely adapted for the preparation of 11C-radiopharmaceuticals in a clinical setting. First, a novel method for the direct formation of 11C-labeled carbonyl groups, where organic bases are utilized as [11C]carbon dioxide-fixation agents. The second method of clinical importance is a low-pressure 11C-carbonylation technique that utilizes solvable xenon gas to effectively transfer and react [11C]carbon monoxide in a sealed reaction vessel. Both methods appear to be general and provide simple paths to 11C-labeled products.ConclusionRadiochemistry is the foundation of PET imaging which relies on the administration of a radiopharmaceutical. The demand for new radiopharmaceuticals for clinical PET imaging is increasing, and 11C-radiopharmaceuticals are especially important within clinical research and drug development. This review gives a comprehensive overview of the most noteworthy 11C-labeling methods with clinical relevance to the field of PET radiochemistry.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.