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Basic Science of PET Imaging for Inflammatory Diseases

ABSTRACT: FDG-PET/CT has recently emerged as a useful tool for the evaluation of inflammatory diseases too, in addition to that of malignant diseases. The imaging is based on active glucose utilization by inflammatory tissue. Autoradiography studies have demonstrated high FDG uptake in macrophages, granulocytes, fibroblasts, and granulation tissue. Especially, activated macrophages are responsible for the elevated FDG uptake in some types of inflammation. According to one study, after activation by lipopolysaccharide of cultured macrophages, the [14C]2DG uptake by the cells doubled, reaching the level seen in glioblastoma cells. In activated macrophages, increase in the expression of total GLUT1 and redistributions from the intracellular compartments toward the cell surface have been reported. In one rheumatoid arthritis model, following stimulation by hypoxia or TNF-?, the highest elevation of the [3H]FDG uptake was observed in the fibroblasts, followed by that in macrophages and neutrophils. As the fundamental mechanism of elevated glucose uptake in both cancer cells and inflammatory cells, activation of glucose metabolism as an adaptive response to a hypoxic environment has been reported, with transcription factor HIF-1? playing a key role. Inflammatory cells and cancer cells seem to share the same molecular mechanism of elevated glucose metabolism, lending support to the notion of usefulness of FDGPET/CT for the evaluation of inflammatory diseases, besides cancer.

SUBMITTER: Toyama H

PROVIDER: S-EPMC7418531 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Project description:Background Many HIV databases and applications focus on a limited domain of HIV knowledge. Since even a “simple” organism like HIV represents a very complex system with many interacting elements, the fractured structure of existing databases and applications likely limits our ability to investigate and understand HIV. To facilitate research, therefore, we have built HIVToolbox, which integrates much of the knowledge about HIV proteins and presents the data in an interactive web application. HIVToolbox allows quick and convenient hypotheses generation, experiment interpretation, and potential new drug structure creation. Methods HIVToolbox was built as a standard three-tier J2EE web application, consisting of 1) an underlying relational MySQL database, 2) a set of standard Java data access objects that pull data from the database, and 3) a set of dynamic web pages the user interacts with. HIV-1 data from external sources such as the Protein Data Bank, NCBI, Los Alamos, etc. was collected, curated, and stored in the HIVToolbox database. Additional data, such as homology and position statistics matrices, was generated from existing data. Since version 1, drug binding site and drug resistant mutation data has also been added. Results HIVToolbox was used to create several new hypotheses about HIV-1 integrase, including predicting the location of a CK2 phosphorylation site, which was later confirmed by experiment. A new version of HIVToolbox support display of the 3D locations of drug resistant mutations on surface plots of HIV proteins and the drug binding sites for structures of complexes of HIV proteins with drugs. Conclusion HIVToolbox is an open-access web application that allows virologists and structural biologists to access detailed information about HIV-1 proteins, such as sequence, structure, functional sites and relationships, homology, drug binding sites, and drug resistant mutations, and to immediately see the relationships between any or all of them. Weblink: [http://hivtoolbox.bio-toolkit.com]

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Basic Science of PET Imaging for Inflammatory Diseases

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